Biomedical subjects

Jody A Summers Rada

Publications and source records attributed to Jody A Summers Rada.

5 recordsLinked to original sources

PubMed2006

Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation.

PURPOSE: The influences of diurnal rhythms involving a variety of ocular parameters are implicated in the development of myopia. The purpose of this study was to determine the expression of the melatonin receptor subtype proteins in chick ocular tissues and to examine the role of the circadian signaling molecule melatonin in normal ocular growth and the exaggerated ocular growth associated with the development of myopia. METHODS: Expression of the Mel(1a), Mel(1b), and Mel(1c) melatonin receptor proteins in ocular tissues was examined by Western blot analyses, slot blot analyses, and immunocytochemistry. For examining the effect of melatonin on ocular growth, chicks were maintained on a 12-hour light-dark cycle and were monocularly form-vision deprived in one eye with a translucent occluder for 5 days. During the 5-day treatment period, chicks were injected systemically during the early dark period with melatonin (0.6 mg) or 2% ethanol vehicle control. Ocular dimensions of normal and deprived eyes were examined by high frequency A-scan ultrasound. RESULTS: Immunocytochemical analysis of chick ocular tissues revealed the cellular distribution of the Mel(1a) receptor subtype in the cornea, choroid, sclera, and retina. Western blot and slot blot analyses demonstrated that all three receptors were present in these tissues and they demonstrated distinct diurnal rhythms of protein expression in the retina-RPE-choroid, with peak levels of Mel(1a) and Mel(1b) occurring during the night and peak levels of Mel(1c) during the day. Systemic administration of melatonin resulted in significant changes in anterior chamber depth, vitreous chamber depth, and choroidal thickness of form-deprived and/or control eyes. CONCLUSIONS: Results of this study show that all three melatonin receptor subtypes are expressed in retinal and extraretinal ocular tissues of the chick eye. The finding that administration of melatonin alters the growth of several ocular tissues in both control and form-deprived eyes suggests that melatonin, acting through specific melatonin receptors in ocular tissues, plays a role in ocular growth and development. This conclusion suggests that the action of melatonin, combined with expression of melatonin receptors, is involved in the regulation of the diurnal rhythm of ocular growth.

Animals↗

PubMed2006

Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets.

PURPOSE: The purpose of this study was to examine the possibility that all-trans-retinoic acid (RA) in the eye is a signal related to changes in scleral extracellular matrix in a primate model of postnatal eye growth. METHODS: Juvenile marmosets (Callithrix jacchus) were divided into two experimental groups based on their response to monocular deprivation with diffusers: group 1, treated eyes becoming longer than fellow control eyes (n = 8), and group 2, treated eyes becoming shorter than control eyes (n = 7). Eyes were enucleated, dissected, and assayed for changes in the rates of scleral glycosaminoglycan (GAG) synthesis and ocular RA synthesis. The rate of incorporation of (35)SO4 into CPC-precipitable GAG in scleras was taken as a measure of the rate of synthesis of proteoglycans. In the same eyes the rate of RA synthesis in vivo was measured separately in the retina and the choroid/RPE (choroid with RPE attached) by HPLC. The effect of RA on the rate of scleral GAG synthesis was also examined in tissue-cultured pieces of sclera from additional marmosets. RESULTS: Induced changes in vitreous chamber length in diffuser-treated eyes correlated inversely with the rate of scleral GAG synthesis (P < 0.05) and directly correlated with the rate of RA synthesis measured separately in the retina (P < 0.05) and the choroid/RPE (P < 0.05). In group 1, the rate of scleral GAG synthesis was significantly lower (P < 0.01) in the treated eyes relative to control eyes, and the rate of RA synthesis in both the retina and the choroid/RPE was significantly higher (P < 0.01). In group 2, the rates of scleral GAG synthesis and RA synthesis in either the retina or choroid/RPE were not found to change significantly in the treated eyes compared with the control eyes. RA partially reduces the rate of scleral GAG synthesis in tissue-cultured primate sclera in a dose-dependent manner after several days. CONCLUSIONS: RA may play a role in the visual control of postnatal eye growth in primates, possibly by inducing changes in scleral extracellular matrix associated with increasing eye size. Decreasing growth rate below control levels may involve other mechanisms.

Animals↗

PubMed2005

The sclera and myopia.

Myopia is a very common ocular problem, affecting perhaps one billion people worldwide. Most myopia is produced by lengthening of the vitreous chamber of the ocular globe. High myopia is characterized by scleral thinning and localized ectasia of the posterior sclera. The sclera is a dense, fibrous, viscoelastic connective tissue that forms the outer coat of the eye and consists of irregularly arranged lamellae of collagen fibrils interspersed with proteoglycans and non-collagenous glycoproteins. Scleral fibroblasts are located between scleral lamellae, and are responsible for synthesizing the extracellular matrix in which they reside. Research highlighted in this review clearly demonstrates that the sclera is not a static container of the eye, but rather is a dynamic tissue, capable of altering extracellular matrix composition and its biomechanical properties in response to changes in the visual environment to regulate ocular size and refraction. Based on these studies, a strategy directed at reversing myopia-associated scleral extracellular matrix remodeling events would be warranted, particularly in cases of high myopia in humans.

Animals↗

PubMed2004

Localization of Mel1b melatonin receptor-like immunoreactivity in ocular tissues of Xenopus laevis.

The circadian signaling molecule, melatonin, is produced by pinealocytes and retinal photoreceptors. In the retina, melatonin is thought to diffuse into the inner retina to act as a paracrine signal of darkness by binding to specific receptors in retinal neurons. The retinal cell locations of the Mel1a and Mel1c melatonin receptor types have been reported, but the localization of the Mel1b receptor, which is the most highly expressed melatonin receptor type in the retina, is unknown. To determine the cellular distribution of Mel1b melatonin receptor protein in the Xenopus laevis retina and other ocular tissues, polyclonal antibodies were raised against a peptide fragment of the X. laevis Mel1b receptor. Western blot analysis of several ocular tissues revealed the presence of one or more immunoreactive bands in the sclera, cornea, lens, retinal pigment epithelium (RPE)/choroid, and neural retina. In the neural retina, the major immunoreactive bands displayed electrophoretic mobilities corresponding to approximately 35, 42, 45, and 80 Kd. Sections of X. laevis eyes were analyzed by immunocytochemistry and confocal microscopy, in combination with antibodies against the Mel1a melatonin receptor, a rod photoreceptor-specific protein, opsin, and two amacrine cell-specific markers, tyrosine hydroxylase (TOH; dopaminergic cells) and glutamic acid decarboxylase (GAD; GABA-ergic cells). Mel1b immunoreactivity was localized to the apical membranes of RPE cells, and punctate Mel1b immunoreactivity was observed in both rod and cone photoreceptor inner segments. Presumptive horizontal cells that ramify in the outer plexiform layer (OPL) were immunoreactive for Mel1b, and were exclusive of the Mel1a immunoreactivity present in the OPL. Neither TOH nor GAD co-localized with the Mel1b immunoreactivity that was present in the inner plexiform layer (IPL), suggesting that Mel1b is not expressed in dopaminergic or GABA-ergic amacrine cells. Mel1b immunoreactivity was observed in ganglion cells of the retina, a population of cells covering the outer surface of the outer fibrous layer of the sclera, and in lens fibers located in the outer regions of the lens. These results suggest that melatonin may influence retinal function by binding to receptors on RPE and photoreceptor cells, and by acting on neurons of the inner retina that do not use dopamine or GABA as a neurotransmitter. Furthermore, melatonin may bind to receptors on cells located in the sclera and lens, perhaps to modify the growth or function of these ocular tissues.

Animals↗

PubMed2004

Interaction of lumican with aggrecan in the aging human sclera.

PURPOSE: Lumican is a keratan sulfate proteoglycan originally identified in cornea, but present in a variety of connective tissues where it presumably regulates collagen fibril formation and organization. The present study was designed to describe the chemical nature of lumican core protein in the aging human sclera. METHODS: Western blot analyses, immunohistochemistry, and immunoaffinity chromatography were used to detect and purify the lumican core protein from tissue extracts from human donors 6 to 89 years of age. Treatment of lumican with chondroitinase ABC, keratanase-I and -II, and/or endo-beta-galactosidase was used to determine the degree of glycosylation of the lumican core protein. RESULTS: Lumican was present in the human sclera as a 70- to 80-kDa core protein with short unsulfated lactosaminoglycan side chains. In addition, on Western blots, a larger >200-kDa species was apparent that was immunologically related to lumican. This high-molecular-weight material increased in scleral extracts with increasing age. The complex was most abundant in unreduced samples, and approximately two thirds of the 70- to 80-kDa lumican core protein was released from the complex on reduction of the scleral extract. Further characterization of the >200-kDa lumican-immunopurified complex indicated that aggrecan (the cartilage proteoglycan) was covalently associated with lumican. CONCLUSIONS: Reducible and nonreducible lumican-aggrecan interactions occur in the scleral extracellular matrix and result in the formation of high-molecular-weight complexes that increase with age. These results represent the first report demonstrating lumican-aggrecan interactions and suggest they may play a role in age-related scleral extracellular matrix changes.

Adolescent↗