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N J Unakar

Publications and source records attributed to N J Unakar.

At least 19 recordsLinked to original sources
PubMed2001

Glutathione peroxidase-1 deficiency leads to increased nuclear light scattering, membrane damage, and cataract formation in gene-knockout mice.

PURPOSE: Previous in vitro studies with transgenic and gene-knockout mice have shown that lenses with elevated levels of glutathione peroxidase (GPX)-1 activity are able to resist the cytotoxic effect of H(2)O(2), compared with normal lenses and lenses from GPX-1-deficient animals. The purpose of this study was to investigate the functional role of this enzyme in antioxidant mechanisms of lens in vivo by comparing lens changes of gene-knockout mice with age-matched control animals. METHODS: In vivo lens changes were monitored by slit lamp biomicroscopy, and enucleated lenses were examined under a stereomicroscope in gene-knockout animals and age-matched control animals ranging in age from 3 weeks to 18 months. Transmission (TEM) and confocal microscopy were performed on different regions of lenses after the mice were killed at various times. RESULTS: Slit lamp images showed an increase in nuclear light scattering (NLS) in gene-knockout mice compared with control animals. TEM revealed changes in the nucleus as early as 3 weeks of age by the appearance of waviness of fiber membranes. With increasing age, there was greater distortion of fiber membranes and distension of interfiber space at the apex of fiber cells compared with control mice. The changes in nuclear fiber membranes were even more dramatic, as observed by confocal microscopy, which was performed on thicker sections. In contrast to the changes in the lens nucleus, the morphology of the epithelium and superficial cortex remained unchanged in knockout animals during the same experimental period, consistent with slit lamp observations. Stereomicroscopy of ex vivo lenses demonstrated a significant increase in opacification in gene-knockout mice relative to control animals of the same age. This effect became evident in mice aged 5 to 9.9 months and persisted thereafter in older animals, resulting in mature cataracts after 15 months. CONCLUSIONS: The results demonstrate the critical role of GPX-1 in antioxidant defense mechanisms of the lens nucleus. The increased NLS appears to be associated with damage to fiber membranes in the nucleus, which is particularly susceptible to oxidative challenge because of the deficiency of GPX-1. It is suggested that the lens membrane changes in the knockout animals may be due to the formation of lipid peroxides, which serve as substrates for GPX-1. Cataract development in gene-knockout mice appeared to progress from focal opacities, apparent at an earlier age, to lamellar cataracts between 6 and 10 months, and finally to complete opacification in animals older than 15 months. This is the first reported phenotype in GPX-1-knockout mice.

Animals↗
PubMed1997

Effect of pretreatment of germanium-132 on Na(+)-K(+)-ATPase and galactose cataracts.

PURPOSE: Recently, we reported that topical administration of 2-carboxyethyl germanium sesquioxide (Ge-132) concurrently with 50% galactose feeding delayed the establishment of mature cataracts and reduced advance glycation product. This study was to determine the effect of pretreatment of Ge-132 on galactose associated morphological changes and Na(+)-K(+)-ATPase activity. METHODS: Young Sprague Dawley rats received topical eye drops four times a day of either saline or Ge-132 seven days prior to the 50% galactose diet and during galactose feeding. At desired intervals the lenses were extracted, photographed and processed for either light microscopy, scanning electron microscopy or the determination of Na(+)-K(+)-ATPase activity. RESULTS: In Ge-132 pretreated lenses as compared to saline pretreated lenses the following results were observed: (a) the galactose-induced morphological alterations in the majority of lenses were delayed and (b) Na(+)-K(+)-ATPase activity was protected. CONCLUSIONS: Our previous and current studies show that in addition to osmotic stress post-translational protein modification, such as glycation, including enzymes may play a role in initiating changes that lead to cataract development. The inhibition of protein glycation by antiglycating compounds, such as Ge-132, delays sugar cataract formation. Currently, we are investigating the status of protein glycation and advanced glycation end products following pretreatment with Ge-132 and the role of Ge-132 on the activities of enzymes such as aldose reductase and Na(+)-K(+)-ATPase.

Animals↗
PubMed1995

Effect of germanium-132 on galactose cataracts and glycation in rats.

Germanium compounds have been shown to be effective in preventing the formation of advanced glycation end-products and for reversible solubilization of glycated proteins. As protein glycation has been proposed to play a role in lens opacification, we initiated studies to evaluate the effects of 2-carboxyethyl germanium sesquioxide (germanium compound 132 or Ge-132) on galactose-induced cataractogenesis. For this study young Sprague-Dawley rats were fed a 50% galactose diet. One group of rats received topical saline and another group was administered Ge-132 in saline four times a day. The lenses were periodically examined with an ophthalmoscope and at desired intervals processed for light and scanning electron microscopy. Our observations, beginning at 3 days and continuing to 21 days of galactose feeding, exhibited the characteristic galactose-induced morphological alterations, which include the formation of vacuoles, cysts, membrane disruption and swelling of fibers and epithelial cells as well as disorganization of the bow in lenses of rats in both groups. However, in the majority of rats administered Ge-132 these alterations were delayed as compared to the lenses of rats administered saline. Our findings show that, although the initiation, progression and pattern of lens opacification in rats receiving saline and Ge-132 were similar, in the majority of lenses the progression and establishment of mature cataracts in the Ge-132 group of rats were delayed. Analysis of the water-soluble and water-insoluble lens-protein fractions for glycated proteins showed increased levels of the Amadori products and advanced glycation related fluorescent products in galactosemic rats treated with saline eye drops. In rats receiving the topical Ge-132 treatment the levels of these glycation products were substantially reduced to levels lower than control values. Prevention of glycation seems to be a mechanism by which cataract progression is delayed.

Animals↗
PubMed1995

Nuclear light scattering, disulfide formation and membrane damage in lenses of older guinea pigs treated with hyperbaric oxygen.

Nuclear cataract, a major cause of loss of lens transparency in the aging human, has long been thought to be associated with oxidative damage, particularly at the site of the nuclear plasma membrane. However, few animal models have been available to study the mechanism of the opacity. Hyperbaric oxygen (HBO) has been shown to produce increased nuclear light scattering (NLS) and nuclear cataract in lenses of mice and human patients. In the present study, older guinea pigs (Initially 17-18 months of age) were treated with 2.5 atmospheres of 100% O2 for 2-2.5-hr periods, three times per week, for up to 100 times. Examination by slit-lamp biomicroscopy showed that exposure to HBO led to increased NLS in the lenses of the animals after as few as 19 treatments, compared to lenses of age-matched untreated and hyperbaric air-treated controls. The degree of NLS and enlargement of the lens nucleus continued to increase until 65 O2-treatments, and then remained constant until the end of the study. Exposure to O2 for 2.5 instead of 2 hr accelerated the increase in NLS; however, distinct nuclear cataract was not observed in the animals during the period of investigation. A number of morphological changes in the experimental lens nuclei, as analysed by transmission electron microscopy, were similar to those recently reported for human immature nuclear cataracts (Costello, Oliver and Cobo, 1992). O2-induced damage to membranes probably acted as scattering centers and caused the observed increased NLS. A general state of oxidative stress existed in the lens nucleus of the O2-treated animals, prior to the first appearance of increased NLS, as evidenced by increased levels of protein-thiol mixed disulfides and protein disulfide. The levels of mixed disulfides in the experimental nucleus were remarkably high, nearly equal to the normal level of nuclear GSH. The level of GSH in the normal guinea pig lens decreased with age in the nucleus but not in the cortex; at 30 months of age the nuclear level of GSH was only 4% of the cortical value. HBO-induced changes in the lens nucleus included loss of soluble protein, increase in urea-insoluble protein and slight decreases in levels of GSH and ascorbate; however, there was no accumulation of oxidized glutathione. Intermolecular protein disulfide in the experimental nucleus consisted mainly of gamma-crystallin, but crosslinked alpha-, beta- and zeta-crystallins were also present.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Lenticular alterations in hypertensive rats.

Cataract development has been reported in Dahl salt-sensitive (DS) hypertensive rats with high-salt intake. An alteration in ionic transport and electrolyte balance has been reported to be associated with hypertension in these animals. A morphological evaluation of the lenses of salt-sensitive 'cataract-prone' (DS) and salt-resistant (DR) control animals is lacking. We undertook this investigation to evaluate changes in lenticular morphology and in systolic blood pressure (SBP) following administration of high-salt. Both DS and DR rats were given high-salt for up to 33 weeks. Lenses were extracted at desired intervals following the initiation of the high-salt diet and processed for light and transmission electron microscopy. Except for some variations between animals, our study showed that DR rats, in general, exhibited normal SBP and relatively normal morphology. In comparison, the lenses of DS hypertensive rats demonstrated the following major changes: (1) some epithelial cells showed multilayering, nodule formation, pyknotic nuclei, swelling of cell organelles, presence of a large number of lysosomes, and distension of intercellular spaces, (2) disorganization of the bow and (3) swelling of fiber cells in the equatorial region. These changes were similar to those observed in precataractous stages during the development of several types of experimentally induced cataracts and indicate an alteration in normal electrolyte balance as well as hyperosmolarity. Changes in ion transport and electrolyte imbalance have been reported in the lenses of DS rats on high-salt diet. These alterations and a defect in the sodium-potassium pump may be responsible for cataract development in these hypertensive rats.

Animals↗
PubMed1993

Aldose reductase inhibitors and galactose toxicity in neonatal and maternal rat lenses.

We reported that in utero galactose-induced cataracts could be inhibited if aldose reductase inhibitors (ARIs) were included in the galactose diet of pregnant rats. These studies involved morphological and cytochemical approaches. We undertook this investigation to evaluate the effects of ARIs in preventing the formation, accumulation and depletion of dulcitol in lenses of in utero galactose exposed neonates and in mothers during and following pregnancy. Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15mg Sorbinil or 1mg Eisai compound E-0722/day/Kg body weight during and following pregnancy. The lenses of neonates and mothers were processed to determine dulcitol concentrations. At parturition there was a significant amount of dulcitol in the lenses of pups and their mothers, which reduced rapidly in the lenses of pups regardless of the diet fed to the nursing mother. While galactose had a cross-placental but not a milk-mediated effect, the ARIs had both cross-placental and milk-mediated effects on dulcitol accumulation and depletion, respectively. The galactose feeding of mothers post-parturition maintained the high lenticular dulcitol concentration and the absence of galactose led to a reduction in lenticular dulcitol. The correlation between dulcitol accumulation and cataract development is discussed.

Aldehyde Reductase↗
PubMed1993

Elemental studies in rat lens during galactose cataract reversal.

Alterations in elemental composition of the normal lens have been reported to accompany galactose cataract development in rats. In this report we present the changes in regional distribution of Na, K, Cl, P, S and Ca during the reversal of galactose-induced cataracts. Elemental X-ray maps of lenses from young female Sprague Dawley rats fed 50% galactose for 20 days were examined at 0, 20, 40 and 90 days following the transfer of galactose fed rats to Purina Rat Chow diet. Reinstatement of normal elemental distribution accompanied the progression of lens transparency. By 90 days on the rat chow diet, K had increased and Na, Cl and Ca had decreased so that a near normal lenticular distribution of these elements was established. The reinstatement of elemental distribution during cataract reversal followed a pattern similar to that observed for alterations during cataract development, initiating near the equatorial surface and expanding centrally. The correlation between the alterations in the distribution of the elements studied and our previously reported morphological investigation of lenses during galactose cataract reversal is discussed in this report.

Animals↗
PubMed1992

Transient elevation of aldose reductase mRNA in lens of rats developing galactose cataracts.

Aldose reductase (AR), a major enzyme in the polyol pathway, is thought to be responsible for accumulation of polyols in lenses exposed to high doses of galactose or glucose, and it may be linked to some of the complications found in diabetes. In this report we examined the level of expression of AR mRNA in lens epithelia undergoing development of galactose cataracts in vivo. The AR mRNA was quantitated by Northern blot hybridization with a [35S]-RNA transcript from a previously described AR cDNA clone. This was done on normal lens epithelia and on epithelia from lens of rats fed a diet of Purina Chow containing 50% galactose for periods of from 6 hr to 20 days. We found AR mRNA to elevate to about 5-fold the control levels by 12-24 hr on galactose, then decrease to the control levels by day 4. The increase in AR mRNA appears to be transitory. The high abundance in AR mRNA by 24 hr on galactose was confirmed by in situ hybridization. At later periods, from 8 to 20 days on galactose, a slow increase in AR mRNA took effect, as we have previously reported. Changes in the levels of galactose and dulcitol between 0 and 96 hr were also quantitated by gas chromatography, showing that there was a significant increase in both galactose and dulcitol occurring throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1992

Expression of c-myc protooncogene in rat lens cells during development, maturation and reversal of galactose cataracts.

It is well established that normal patterns of epithelial cell proliferation and metabolism, and of fiber cell differentiation and maturation are essential for the maintenance of transparency in the ocular lens. Several factors, including exposure to high levels of sugars, have been known to result in the compromise of lens transparency. For example, initiation of lens cell damage by galactose induces lens epithelial cells to proliferate. Elevated levels of c-myc mRNA have usually been correlated with rapid cell growth and increased entry of cells into the S phase. Therefore, changes in c-myc mRNA levels may provide an early indication of the stimulation of lens epithelial cells to proliferate and differentiate, which has been postulated to be an early and important event in response to lens cell injury by galactose. By Northern blot hybridization analysis we quantitated c-myc mRNA levels in the lens capsule epithelia of rats (1) exposed to galactose, and (2) undergoing a partial recovery from the galactose-induced cell damage. At the onset of lens cell damage, we find c-myc mRNA to elevate to 6-fold by 24 hr, and by 48 hr decreases to about 3-fold the normal levels. During recovery, c-myc mRNA continues to be expressed at high levels approaching a 10-fold increase by day 12, then decreasing to levels of about 8-fold the control by day 30. The 24 h transitory elevation in c-myc mRNA in lens epithelial cells is in accord with our previous observations on the 24 h increase in MP26, gamma crystallin and aldose reductase mRNAs following a high influx of galactose. Therefore, the elevation in c-myc mRNA as well suggest that galactose appears to cause lens cells to undergo an early transitory period of gene induction following the exposure of lens cells to galactose.

Animals↗
PubMed1992

Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats.

We have shown that galactose cataract development is delayed or inhibited with the administration of aldose reductase inhibitors (ARIs). Dulcitol forms and accumulates in the lens of rats fed galactose. We undertook investigations to study the effectiveness of ARIs in preventing the formation and accumulation of dulcitol in the lens. Young Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15 mg sorbinil, 0.15, 0.5, or 1.0 mg E-0722/day/Kg body weight. At desired intervals following the initiation of diets, the lenses were processed for the determination of galactose and dulcitol levels. The lenticular dulcitol increased significantly in all animals fed galactose reaching a maximum level by approximately 15 days with comparatively lower levels in the groups fed ARIs with galactose; this increase was dose dependent in the groups fed E-0722. There was a subsequent, rapid drop in lenticular dulcitol by 18 days in all dietary groups. Interestingly, a second peak of increased lenticular dulcitol was observed in all groups. The correlation between dulcitol accumulation and cataract development is discussed.

Aldehyde Reductase↗
PubMed1992

Alterations in lens permeability during galactose cataract development in rat.

Lens permeability has been shown to be compromised during galactose-induced cataract development in rats. Recent studies have demonstrated permeability and diffusion pathways as well as endocytotic activity in normal lenses of different species using tracers of different molecular weights. We investigated the permeability and diffusion of tracers in normal rat lenses and in lenses during cataract development using three different molecular weight tracers, lanthanum nitrate (LN, MW 430), ruthenium red (RR, MW 858.5) and horseradish peroxidase (HRP, MW 40.000) for this study. Sprague Dawley rats weighing 50gms were fed Purina Rat Chow with or without galactose. Our results, based on transmission electron microscopy, show that all tracers penetrated through the capsule and the basal portion of the intercellular spaces. While the diffusion of RR was restricted to the epithelial cell layer, LN and HRP were observed in intercellular spaces in cortical fiber cells. In the HRP "washout" studies, HRP could be readily removed from the intercellular spaces in the basal region in the epithelial cell layer. This and other observations suggest the presence of a barrier (tight-junction) in the apical region. Our studies also suggest an influx of tracers in the lens, specifically LN and HRP, through the equatorial region. The permeability of the tracers increased and endocytotic vesicles with tracers were often found associated with the lateral and basal membranes of epithelial cells in the galactose-fed rats at the precataractous and mature cataractous stages. This study provides further support for the presence of a tight-junction between epithelial cells and indicates the movement of tracers through the equatorial region. Moreover, it confirms previous observations that indicated alterations in lens permeability during galactose cataractogenesis.

Animals↗
PubMed1991

Evaluation of lens epithelial cell differentiation by quantitation of MP26 mRNA relative to gamma-crystallin mRNA in initiation of galactose cataracts in the rat.

It is well established that in response to feeding of galactose to four-week-old rats cataracts develop (Unakar, Genyea, Reddan & Reddy, Exp. Eye Res. 26, 123-33, 1978). Initiation of cataracts leads to epithelial cell proliferation. In the lens, the main intrinsic membrane protein, MP26, is recognized as a fiber cell-specific gene product, and gamma-crystallin is found in terminally differentiated fiber cells. By Northern blot analysis we quantitated the MP26 and gamma-crystallin mRNAs found in the lens at various times spanning from 0 to 96 hr on galactose. We find that by 24 hr, MP26 mRNA, as well as gamma-crystallin mRNA, increased significantly above the zero time levels. The data was also confirmed by in situ hybridization of various lens sections to both gamma-crystallin and MP26 35S-labeled antisense RNA probes. As expected, at later periods beyond 24 hr, the levels of gamma-crystallin and MP26 mRNAs dropped to below the control levels. The initial increase in MP26 and gamma-crystallin mRNAs lead us to conclude that initiation of galactose cataracts appears to support, although for a short time period, both epithelial cell elongation and fiber cell differentiation.

Animals↗
PubMed1991

In utero and milk-mediated effect of aldose reductase inhibitor on galactose cataracts.

Our previously reported investigations showed that cataracts could be induced in fetal lenses through the maternal feeding of galactose during pregnancy. We also reported that the lens opacity present at birth reverses completely by 30 days of age if there is no further post-natal exposure to galactose. This investigation was designed to investigate if an aldose reductase inhibitor (ARI) has any cross-placental effect in preventing galactose-induced cataracts in fetuses. We have also evaluated if there are any milk-mediated effects of galactose on cataract induction and of galactose and ARI on the maintenance or reversal of opacities induced in utero. Pregnant Sprague-Dawley rats were fed either 50% galactose or rat chow with or without the ARI, (2R,4S)-6-fluoro-2-methyl spirochroman-4,4'-imidazolidine-2',5'-dione (Eisai compound E-0722). Following parturition, pups of mothers from the different dietary groups were either fed by their own mothers or foster fed by lactating females fed either rat chow or 50% galactose with or without the ARI. Lenses of the pups were examined at desired intervals with light and scanning electron microscopes. We observed that: (a) both galactose and the ARI had a cross-placental effect on the fetal lenses in the development and inhibition of cataracts, respectively; (b) galactose had very little, if any, milk-mediated effect on either the induction of cataracts in newborn pups that were born with transparent lenses or the maintenance of cataracts induced in utero; (c) the ARI appeared to have a milk-mediated effect, which accelerates the reversal of cataract associated alterations in lenses of pups with cataracts induced in utero, leading to further reinstatement of lens transparency; and (d) the presence of ARI in the diet of rats during pregnancy and/or post-parturition provided continued protection to the lenses of pups that were exposed to a galactose diet following birth.

Aldehyde Reductase↗
PubMed1991

Crystallin mRNA concentrations and distribution in lens of normal and galactosemic rats. Implications in development of sugar cataracts.

It is well established that high concentrations of sugar in the lens of the eye eventually lead to fiber cell destruction and cataracts. In these studies the decrease in crystallin mRNAs was quantified as a result of influx of high concentrations of galactose into the lens of rats. The alpha A-, alpha B1-, and gamma-crystallin mRNA concentrations were assessed in normal lens and in lens undergoing development of sugar cataracts by northern blot and in situ hybridization methods. In a normal, 28-day-old lens, alpha A-crystallin mRNA accumulated to high levels throughout the fiberplasm, and alpha B-crystallin mRNA was present at low levels in epithelial cells, with increased expression in elongating epithelial and fiber cells. The beta B1-crystallin mRNA was distributed to about the same grain density throughout the fiberplasm but at significantly lower levels than alpha A-crystallin mRNA. The gamma-crystallin mRNA first emerged in the terminally differentiated fiber cell, with insignificant amounts detected in the elongating epithelial and fiber cells at the bow. Measurements of hybridization levels on the same RNA population isolated from a single lens showed that in the controls, alpha A-crystallin mRNA comprised about ten times the level of alpha B-crystallin mRNA and twice the level of beta B1- and gamma-crystallin mRNAs. In the cataractous lens the rate of decrease in the concentrations of alpha A-, alpha B- and beta B1-crystallin mRNAs was the same; the decrease in gamma-crystallin mRNA was far more severe. By 20 days of feeding of galactose, at the age of 48 days, gamma-crystallin mRNA diminished to about 9% of the control levels, alpha A-crystallin mRNA to 49%, alpha B-crystallin mRNA to 55%, and beta B1-crystallin mRNA to 65%. In the normal lens, at 48 days of age, the levels of alpha A-, alpha B-, and beta B1-crystallin mRNAs showed no significant changes; the gamma-crystallin mRNA level decreased significantly, to about 70% of the day-28 level, the time at which galactose feeding began. Overall, these data suggest that the loss in crystallin mRNAs in response to the development of galactose cataracts follows this order of decline: gamma greater than alpha B greater than alpha A greater than beta B1.

Animals↗
PubMed1991

Permeability studies in neonatal rat lens epithelium.

Lanthanum nitrate (LN) and horseradish peroxidase (HRP) were used as tracers to study intercellular permeability as well as the existence and location of tight junctions and changes in them, if any, in the lens epithelium of Sprague Dawley rats. Thin sections of lenses taken from animals at birth and at three day intervals until the neonates were weaned at approximately 22 days were studied at the electron microscope level. At every age both tracers permeated the intercellular spaces of the anterior region epithelium and between the fiber cells of the equatorial region. The LN precipitates terminated near the apical part of the epithelium in the anterior polar region and were not seen at the epithelial-fiber interface or between fibers in this region. At the site of the tracer termination the intercellular space was found to be considerably constricted or completely sealed. The HRP precipitates, however, were present in these intercellular spaces and by using the HRP "washout" procedure could be washed out of the basolateral site of the intercellular spaces of the epithelium up to the point of constriction if a tight junction were present. The lens area occupied by epithelium with tight junctions was age related being very small in lenses from animals less than 24 hours old and becoming increasingly enlarged as the newborn aged. These findings further confirm the existence of a barrier in the form of tight junctions between epithelial cells in the central anterior region of the maturing rat lens. Moreover, our observations also provide information regarding the pattern of tight junction development and distribution during lens maturation.

Animals↗
PubMed1990

Management of aldose reductase mRNA abundance in rat lens undergoing reversal of galactose induced cataracts. A model for gene response to changes in the environment.

Aldose reductase (AR) mRNA concentration in rat lens was quantitated by hybridization of a RNA transcript from a previously described AR cDNA clone to mRNA found in epithelial and cortical cytosols. This was done on normal rat lens and on lens initially made cataractous by feeding of a diet of Purina Chow containing 50% galactose, followed by reversal of the cataracts due to the removal of the galactose from the diet. Recent data from this laboratory has shown that AR mRNA was increased in lens epithelial cells upon administration of galactose; while in the cortex it was reduced to insignificant levels when fiber cell damage became extensive by day 20 on galactose. Present data reveals that, upon removal of galactose from the diet, the lens epithelial AR mRNA was gradually reduced from the high levels found at day 20 of galactose feeding to low levels by day 30 of reversal. On the other hand, the cortex exhibited an initial sudden increase in AR mRNA at days 1 to 6 of reversal and by day 30 it was reduced to levels below those found in the untreated lens. DNA content in the epithelium also began to decrease to normal levels by day 16 following reversal of the cataracts. The data demonstrate that the concentration of AR mRNA in lens of reversed cataracts appears to faithfully reflect the loss of epithelial cellular need for AR mRNA in favor of enhanced differentiation of epithelial cells to secondary fiber cells.

Aldehyde Reductase↗
PubMed1990

Aldose reductase mRNA is an epithelial cell-specific gene transcript in both normal and cataractous rat lens.

Aldose reductase (AR) is implicated in the development of sugar cataracts by its reduction of galactose or glucose to polyols. The authors' recent work suggested that AR mRNA is found to be expressed in high concentrations in rat-lens epithelial cells after exposure of the animal to a diet containing 50% galactose. They localized the AR mRNA in the lens cells by in situ hybridization with a previously described AR clone. The data establish that AR mRNA is apparently an epithelial and not a fiber-cell gene transcript. It accumulates in the epithelial cell, then it is carried into the newly differentiated fiber cell, and finally it concentrates in the posterior region of the matured fiber cell. The AR mRNA is found in all of the anterior epithelial cells including the equatorial and central epithelia. It is present at highest concentrations in the elongating epithelial cells, and it is distributed equally throughout the secondary fiber cells at the bow, with no indication of a preferential buildup of AR mRNA in any of the nucleated fiber cells in the cortex. This differs from what the authors reported to occur with MP26 mRNA, a fiber cell-specific gene transcript. They found that MP26 mRNA was absent from the epithelial cells but was preferentially found in the secondary fiber cells. Present data suggest that the increase in AR mRNA concentration observed to occur in cataractous lenses is a result of epithelial cell proliferation, where every cell appears to be competent in expressing AR mRNA. The results of this research imply that AR mRNA is a lens epithelial cell-specific gene transcript in both normal and cataractous lenses.

Aldehyde Reductase↗