Biomedical subjects

J V Jester

Publications and source records attributed to J V Jester.

At least 91 records · Page 5Linked to original sources

PubMed1992

Effects of increasing Dk with rigid contact lens extended wear on rabbit corneal epithelium using confocal microscopy.

The effects of 24-h wear of various Dk-rigid gas-permeable (RGP) contact lenses on the rabbit corneal epithelium were studied by in vivo tandem scanning confocal microscopy (TSCM), and confirmed by scanning electron microscopy (SEM). Lenses used were polymethylmethacrylate (PMMA) (Dk/L = 0), RGP experimental A lens (siloxanylmethacrylate-fluoromethacrylate-methylmethacrylate , 33), experimental B (siloxanylmethacrylate-fluoromethacrylate, 56), and experimental C (siloxanylstyrene-fluoromethacrylate copolymer, 64 x 10(-9)) (cm/s) (ml O2/ml mm Hg) with 0.15-mm thickness (Dk/L measured by polarograph including boundary layer effect). After 24-h PMMA lens wear, TSCM showed no superficial epithelial cells but only exposed, underlying wing cells. The cornea with experimental A showed partial superficial epithelial desquamation. With experimental B wear, slight superficial epithelial cell swelling and desquamation were observed on the surface of the cornea. No changes were observed for the eye with experimental C and control. The observed severity of desquamation of superficial epithelial cells was dependent on the oxygen transmissibility (Dk/L) of RGP lenses worn. All in vivo findings were confirmed by SEM observations. Based on the results of this study, we conclude that (a) although Dk/L = 56 lens B shows no residual overnight corneal swelling, surface damage is still produced; (b) Dk/L = 64 lens C is best for epithelium showing the same corneal images as control; and (c) TSCM is a good way to evaluate the contact lens safety and efficacy in vivo at the cellular level noninvasively.

Animals↗

PubMed1992

Digital image acquisition in in vivo confocal microscopy.

A flexible system for the real-time acquisition of in vivo images has been developed. Images are generated using a tandem scanning confocal microscope interfaced to a low-light-level camera. The video signal from the camera is digitized and stored using a Gould image processing system with a real-time digital disk (RTDD). The RTDD can store up to 3200 512 x 512 pixel images at video rates (30 images s-1). Images can be input directly from the camera during the study, or off-line from a Super VHS video recorder. Once a segment of experimental interest is digitized onto the RTDD, the user can interactively step through the images, average stable sequences, and identify candidates for further processing and analysis. Examples of how this system can be used to study the physiology of various organ systems in vivo are presented.

Animals↗

PubMed1992

Comparison of in vivo and ex vivo cellular structure in rabbit eyes detected by tandem scanning microscopy.

Using the tandem scanning microscope, in vivo confocal microscopic images of living eyes were compared to images obtained from ex vivo, freshly enucleated or fixed tissue in the rabbit. In the normal cornea, microscopic details of the superficial epithelium, basal lamina, stromal fibrocyte nuclei, nerves and endothelial cell borders were easily discernible. Removal of the eye from the intact animal resulted in loss of detail with distortion of the normal structural interrelationships within the corneal stroma whilst enhancing details of the corneal epithelium. Formalin fixation further enhanced details of the basal and suprabasal corneal epithelial cell nuclei and the stromal fibrocyte cell borders whilst inducing prominent brightly reflecting folds in the thickened stroma with concomitant enhancement of the edge contrast of the collagen lamellae. These changes appeared to be related, in part, to hydration of the cornea and artefactual pooling of water between structures that may enhance reflectivity by increasing the difference between the refractive index of the cellular and extracellular elements. We conclude that microscopic examination of ex vivo preparations of corneal tissue, although providing increased resolution similar to conventional light microscopic techniques, significantly altered the normal structural relationships and could lead to erroneous measurements of the physiological properties of the tissue as compared to in vivo microscopy of undisturbed, intact tissue.

Animals↗

PubMed1992

Radial keratotomy. 1. The wound healing process and measurement of incisional gape in two animal models using in vivo confocal microscopy.

Using in vivo confocal microscopy, corneal wound healing was evaluated in both rabbit and cat eyes after radial keratotomy. A total of six rabbit and six cat eyes were evaluated sequentially over time for 1 mo after surgery by in vivo confocal microscopy, and quantitative measurements of changes in incisional wound gape were determined. In vivo histopathologic changes were correlated with conventional histopathologic findings in 18 rabbit and 4 cat eyes; the animals were killed at various intervals from 0-30 days after surgery. In the rabbit, in vivo corneal wound healing was characterized by the initial ingrowth of corneal epithelium followed by persistence within the wound without a marked fibrotic response. Measurement of incisional wound gape showed increasing gape from 144 +/- 32 microns on day 0 to 976 +/- 155 microns on day 26 at a distance of 2.4 mm from the optical zone. These in vivo measurements were not significantly different (P = 0.996) from those obtained using conventional histopathologic techniques which showed an incisional wound gape of 252 +/- 112 microns on day 0 and 917 +/- 216 microns on day 26 at 2.5 mm from the optical zone. In the cat eyes, healing of radial keratotomy wounds showed an initial increase in incisional wound gape from 135 +/- 56 microns on day 0 to 245 +/- 88 microns on day 7 at a distance of 2.4 mm from the optical zone. Starting at day 14 and continuing to day 30, there was a progressive decrease in incisional wound gape from 198 +/- 41 microns to 92 +/- 35 microns. Sequential, in vivo histopathologic analyses indicated that increasing incisional wound gape correlated with the retention of corneal epithelium in the wound. Initiation of decreasing incisional wound gape was associated with replacement of the incisional epithelial plug with fibroblastic tissue. These changes in the incisional wound gape observed in the cat suggest that healing of radial keratotomy wounds involves contraction of the wound in response to the ingrowth of fibroblastic cells. Furthermore, the contractile response appears to be biphasic involving a precontractile and contractile phase. Overall these data indicated that in vivo confocal microscopy provides quantitative histopathologic data on living tissue comparable with that obtained with conventional techniques on dead, fixed, and sectioned tissue. Additionally, the absence of wound fibrosis in the rabbit radial keratotomy model raises important questions as to the appropriateness of this experimental model for human radial keratotomy.

Animals↗

PubMed1992

Radial keratotomy. II. Role of the myofibroblast in corneal wound contraction.

The cellular mechanism of corneal wound contraction after radial keratotomy (RK) was studied in a feline eye model. A total of 10 cat eyes were evaluated at various times from 0-30 days after surgery. Changes in the distribution of intracellular filamentous actin, nonmuscle myosin, alpha-actinin, surface membrane alpha 5 beta 1 integrin, and extracellular fibronectin were studied using immunofluorescence and laser confocal and electron microscopy. From day 3-7, staining for fibronectin increased along the wound margin. By day 7, keratocytes adjacent to the wound margin showed increased f-actin staining with intense staining for fibronectin compared with normal keratocytes. Myosin and alpha 5 beta 1 integrin expression was very weak at this time; alpha-actinin was not found. By day 14, fibroblasts within the wound formed f-actin microfilament bundles (stress fibers) which colocalized with fibronectin. Wound-healing fibroblasts also stained positively for alpha 5 beta 1 integrin, myosin, and alpha-actinin (the latter two were colocalized). The presence of myosin and alpha-actinin in the wound fibroblasts and the re-organization of f-actin into stress fibers by day 14 correlated with the development of wound contraction. A comparison of the cellular distribution of actin, myosin, and alpha-actinin with alpha 5 beta 1 integrin 14 days after injury suggested that integrin was localized along stress fiber bundles during wound contraction. The data from this study suggest that modulation of wound gape during healing of RK wounds may involve transformation of the corneal keratocyte to a myofibroblast-like cell and the subsequent formation of intracellular stress fibers composed of f-actin, nonmuscle myosin, and alpha-actinin. Based on the colocalization of fibronectin filaments and f-actin filaments and the unique distribution of alpha 5 beta 1 integrin, these findings support the hypothesis that the tension within the wound is generated by the formation of intracellular stress fibers and the interactions between stress fibers and the extracellular matrix, mediated by specific membrane receptor molecules.

Animals↗

PubMed1992

Radial keratotomy. III. Relationship between wound gape and corneal curvature in primate eyes.

The relationship between changes in wound gape and corneal curvature after radial keratotomy (RK) was evaluated in five primates. Four-incision RK was performed using a diamond knife set to 100% of central corneal thickness with a 3-mm optical zone. In vivo measurements of wound gape were obtained using tandem scanning confocal microscopy at 3, 7, 14, and 45 days after surgery. The changes in corneal contour were measured at the same time points using a corneal modeling system with a specially designed primate cone. Wounds progressively increased in width to a maximum of 38 +/- 1 microns (n = 5) at day 7. After day 7, wounds showed increasing fibrosis which correlated with decreasing wound gape to 20 +/- 1 microns at day 45. A similar temporal change was detected in central corneal curvature (K), with maximum flattening occurring at day 7 (delta K = -3.17 +/- 0.90 diopters, n = 5), and progressive regression of effect to -1.32 +/- 0.61 diopters (n = 5) at day 45. Although there was interanimal variation, the mean temporal changes in corneal curvature significantly paralleled the changes in wound gape (r = -0.96, n = 4, P < 0.05). Based upon these findings, a simple geometric model was proposed which provides a hypothetic foundation for the relationship between corneal curvature and wound gape after RK. Calculations of wound gape made from this analytic model (using the measured topographic data) showed significant correlation with the actual wound gape measurements (r = 0.96, n = 4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Variations in corneal wound healing after radial keratotomy: possible insights into mechanisms of clinical complications and refractive effects.

Ultrastructural and histopathologic analysis was performed on three human corneal specimens for variable and complicated refractive outcomes 1-2 years after radial keratotomy. Specimens were obtained immediately postsurgery after microkeratome resection with homoplastic lamellar keratoplasty (two cases) and penetrating keratoplasty (one case) for correction of glare, severe astigmatism, overcorrection, and/or double vision. All three cases showed variability of wound healing and delayed corneal wound healing sites; epithelial retention cysts, and/or absence of stromal scar collagen that was not dependent on the length of time after surgery. Two of the three radial keratotomy specimens also contained extensive duplication of the superficial corneal epithelial basal lamina. When present, the thickened basal lamina (3-6 microns in thickness) was seen between all incisions evaluated and appeared to extend from the central optical zone out to the periphery of the lamellar button. The one full-thickness keratoplasty specimen showed focal loss of underlying endothelial cells with occasional migrating cells seen by scanning electron microscopy. These data support previous findings that delayed corneal wound healing with epithelial retention cysts remains the most common histopathologic alteration after radial keratotomy. The effects of variations and delay in wound healing between individuals could explain the lack of predictability of refractive outcome and continuing refractive instability in long-term follow-up after single or repeat radial keratotomy surgeries.

Adult↗

PubMed1992

Confocal microscopic studies of living rabbit cornea treated with benzalkonium chloride.

The effects of benzalkonium chloride (BAK) on the living rabbit cornea were studied by in vivo Tandem scanning confocal microscopy (TSCM) and confirmed by conventional scanning electron microscopy (SEM). Two drops of saline or phosphate-buffered saline (PBS) containing BAK in concentrations of 0.02, 0.01, and 0.005% was applied to rabbit eyes 15 times at 5-min intervals. The solutions were pH 5.5-5.9 (saline) and pH 7.5 (PBS), and osmolarity was 275-280 (saline) and 300-307 mOsm (PBS). Immediately after application of 0.02 and 0.01% BAK, no normal corneal superficial epithelial cells could be imaged by in vivo TSCM. No swelling of the superficial epithelial cells was observed for the control solution without BAK; however, there was a small amount of desquamation. Application of as little as 0.005% BAK caused the superficial epithelial cells to swell and desquamate. The observed desquamation of corneal superficial epithelial cells increased with higher BAK concentrations applied to the eye. One hour after final drug application, inflammatory cells appeared on the surface of the cornea treated with 0.02% BAK. These findings were correlated with SEM observations. Based on the results of this study, we believe that BAK used frequently can produce clinical corneal toxicity and that the cytotoxicity of any topical ophthalmic solutions can be evaluated by in vivo TSCM.

Animals↗

PubMed1991

Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys.

Tandem Scanning Confocal Microscopy (TSCM) allows one to section optically into and record real-time images of living organs and tissues in a noninvasive fashion. In this paper, we will present some initial TSCM observations of subcapsular nephrons in the living, intact kidneys of Munich-Wistar rats and evaluate the nephron's responses to temporary ischemia and to intravenous infusion of mannitol. The rats were anesthetized with Inactin and a laparotomy performed to expose the kidneys. Using a TSCM equipped with a 20 x water-immersion objective, we optically sectioned through the intact kidney capsule and recorded real-time images of living subcapsular glomeruli and uriniferous tubules. The proximal tubule brush border was highly reflective and allowed us to distinguish between the first and second segments of the proximal tubules as well as the distal tubules. Cellular elements of the blood could be seen passing rapidly through peritubular capillaries and individual glomerular capillary loops. With fluorescent filters in place, intravenously injected carboxyfluorescein was seen to pass through the glomerular capillary loops and then progressively through the different segments of the uriniferous tubules. Ligation of the renal artery resulted in rapid swelling of proximal tubule cells into the tubular lumens, loss of reflectiveness of the microvillous brush borders, and closure of the peritubular capillary spaces. Upon release of the ligature, the proximal tubule lumens again became patent, often opening up abruptly and in a zipper-like fashion down the length of the tubules. Increasing the glomerular filtration rate by intravenous infusion of mannitol resulted in increases in tubular luminal and perimeter dimensions. Mannitol also acted as an effective impermeant osmotic agent and prevented most of the cellular swelling which was otherwise seen in response to renal ischemia.

Animals↗

PubMed1991

In vivo, real-time confocal imaging.

We have adapted a tandem scanning confocal microscope for real-time, non-invasive imaging of cells under in vivo conditions. This form of in vivo confocal imaging relies on the optical sectioning abilities of the confocal microscope to obtain en face, sequential, reflected light images of cells at various depths, up to 1 mm, within opaque organs in living animals. Of major consideration in the design of an in vivo confocal microscope is maximizing the real-time detection of signals reflected from low contrast structures which can be affected by the microscope design, objective, and image detector systems. Using an in vivo confocal microscope design with a 20 x BioOptics surface contact objective we have obtained live cellular images from selected tissues including cornea, kidney, liver, adrenal, thyroid, epididymis, and muscle and connective tissue of rabbits and rats. Images were captured, digitized, and processed using a DAGE Mti low light level SIT camera coupled to a Gould IP9527 image processor. In vivo images were also compared with conventional bright field light and scanning electron microscopic images of "dead," fixed tissues. Overall, in vivo confocal imaging can provide remarkable detail of living cells comparable to that of conventional microscopic images of "dead," fixed, and stained tissue. A more unique feature of in vivo confocal imaging is the ability to study cellular structure and function sequentially over time in the same organ or tissue and represents a fundamentally new paradigm in microscopy. With continued refinements in the microscope, objective and detection system designs and their consequent improvements in lateral and axial resolution, in vivo confocal microscopy will enable us as observers to see what no one has been able to see before.

Animals↗

PubMed1991

Meibomian gland dysfunction in chronic blepharitis.

We examined 57 patients with symptoms of chronic blepharitis using meibomian gland expression, meibography, tear osmolarity, and the Schirmer's test. We also performed meibography on 20 normal patients free of chronic blepharitis. We found that 42 blepharitis patients (74%) had evidence of meibomian gland loss, whereas only four of 20 normal patients (20%) had any gland dropout. We performed cluster analysis on the data from the patients with blepharitis and found that these patients tended to fall into distinct groups with clinically relevant characteristics. We also found that tear osmolarity correlated positively with gland dropout (+0.413) and negatively with excreta volume (-0.499). This study demonstrates that an objective analysis of meibomian gland function may be used to assess chronic blepharitis and define subsets of blepharitis with measurable differences. It also supports the significance of meibomian gland dysfunction on tear osmolarity and the evaporative state of the eye.

Adult↗

PubMed1991

Meibomian gland morphology and tear osmolarity: changes with Accutane therapy.

We evaluated the meibomian gland function of 11 patients before and during treatment with isotretinoin (Accutane) by assessing tear osmolarity, meibomian gland morphology, tear production, rose bengal staining, and meibomian gland excreta. We found, during Accutane use, that meibomian glands appeared significantly less dense and atrophic by meibography. Excreta thickness increased from 1.7 +/- 0.9 to 3.1 +/- 1.2 (p less than 0.005), and expressible excreta volume decreased from 1.52 +/- 0.68 to 1.10 +/- 0.3 (p less than 0.05) (scale 1-4). We also found a significant increase in tear osmolarity from 304.9 +/- 11 to 316.3 +/- 10 mosmol/L (p less than 0.005). There was no significant change in the Schirmer test during treatment. We suggest that the clinical symptoms of blepharitis during Accutane therapy are related to decreased meibomian gland function and consequent increased tear evaporation and tear osmolarity.

Acne Vulgaris↗

PubMed1990

Comparison of corneal epithelial wound healing rates in scrape vs. lamellar keratectomy injury.

Previous in vivo studies evaluating the effects of growth factors on epithelial regeneration have used the scrape injury model in rabbit eyes. Since growth factors act principally on the mitotic activity of regenerating cells, the rapid wound closure rates following scrape injury may not adequately access the effects of these agents on epithelial repair. In this study, we evaluated the rates of wound healing following scrape (8.6 mm) and lamellar keratectomy (8.6 mm) injury in 25 albino rabbits. Eyes were left untreated or received daily application (two to three times) of (a) Tears Naturale II, (b) 50 mM Tris/NaCl, and (c) commercial vehicle for EGF. Eyes were evaluated daily by fluorescein staining with Ophthalmic Fluoro-Strips followed by clinical photography. The area of staining was quantitated by computer-assisted planimetry and rates calculated by linear regression analysis. Eyes receiving scrape injuries epithelialized by 3 days following surgery. Rates of wound closure in two separate groups (six eyes each) were 25.83 mm2/day (r = 0.96) and 29.56 mm2/day 9r = 0.97). Lamellar keratectomy injuries epithelialized by 7 to 8 days, which is substantially longer than that observed for scrape injuries. Rates of wound healing in two separate untreated groups (8 and 10 eyes) were 10.88 mm2/day (r = 0.95) and 9.00 mm2/day (r = 0.93), respectively, which were not significantly different. Analysis of variance comparing rates of wound closure indicated that lamellar keratectomy injuries heal at a significantly slower rate when compared to scrape injury (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epithelium: keratin markers for an alternative pathway of keratinocyte differentiation.

Cultured rabbit corneal epithelial cells undergo three distinct stages of growth and differentiation characterized by the sequential appearance of K5/K14 keratin markers for basal keratinocytes, K6/K16 keratin markers for "hyperproliferative" keratinocytes, and K3/K12 keratin markers for corneal-type differentiation. Analyses of [35S]methionine-labeled, newly synthesized keratins revealed that K6/K16 are synthesized only briefly when the cells undergo exponential growth, and their synthesis is suppressed when the cells reach confluence and switch to synthesizing K3/K12. Transient synthesis of K6/K16 was also observed in vivo during corneal epithelial regeneration. Although K6/K16 expression in general correlates well with cellular growth, drug-induced inhibition of corneal epithelial growth and related data on human epidermal keratinocytes indicate that these two events are dissociable. These results establish clearly for the first time a reciprocal relationship, on a protein level, between the synthesis of K6/K16 and a differentiation-related keratin pair, K3/K12. Such a relationship strongly suggests a competitive mechanism controlling the synthesis of these two major classes of keratins in the suprabasal compartment. Our results also indicate that although hyperproliferation is usually accompanied by K6/K16 expression, the reverse is not always true. Taken together, the data suggest that K6/K16 are synthesized, perhaps by default, as an alternative suprabasal keratin pair under conditions that are nonpermissive for keratinocytes to express their normal, differentiation-related keratin pairs.

Animals↗

PubMed1989

Meibomian gland dysfunction. I. Keratin protein expression in normal human and rabbit meibomian glands.

The expression of keratin proteins from meibomian glands and their correlation with skin epidermal keratins were determined. Keratin proteins were localized in both human and rabbit meibomian glands by indirect immunofluorescence using mouse monoclonal antibodies AE1, AE2 and AE3, which are known to react with human epidermal keratins as well as with keratins from other sources. Keratin proteins from rabbit meibomian glands were further isolated and characterized by SDS-PAGE and immunoblot using mouse monoclonal antibodies AE1 and AE3. Meibomian glands from human and rabbit showed similar immunofluorescent staining with each monoclonal antibody. AE1 antibody, which stains human basal epithelial cells of skin, stains all duct epithelial cells in the human but only the superficial duct epithelial cells in the rabbit meibomian gland. AE2 antibody, which stains human suprabasal epithelial cells of skin and is a marker for fully keratinized epithelia, stains the suprabasal epithelial cells of the central duct and ductules in both the human and rabbit meibomian gland. AE3 antibody, which stains all human epithelial cells of skin, stains all epithelial cells of the duct and ductules, as well as the basal epithelial cells of the acinus in both the human and rabbit meibomian gland. Keratins isolated from whole rabbit meibomian glands contained a 65-67 kD and 58 kD AE3-positive, and a 56.5 kD and 50 kD AE1-positive keratin protein. Expression of 65-67 kD/56.5 kD keratin proteins, and the immunofluorescent staining of the duct epithelium by the AE2 antibody, indicate that the meibomian gland duct epithelium is committed to the process of keratinization.

Animals↗

PubMed1989

Meibomian gland dysfunction. II. The role of keratinization in a rabbit model of MGD.

Meibomian gland dysfunction (MGD) was induced in 34 albino rabbits by the twice-daily topical application of 2% epinephrine over a period of 6 months to 1 year. Seven age-matched control rabbits, not receiving epinephrine, were followed up for a similar period. All lids were evaluated pre- and post-treatment by gross clinical examination and by transillumination biomicroscopy and photography. Of the 68 rabbit lids evaluated, 56% developed signs of MGD, which ranged from plugging of the meibomian gland orifice and presence of microcysts (subclinical lesions; 30.9% of the lids) to opacification and enlargement of the glands with increasing severity (clinical lesions; 25.0% of the lids). The remaining lids (44%) remained normal. MGD did not develop in the seven control rabbits. After the development of MGD, lids were evaluated by immunofluorescent microscopy, SDS-PAGE and Western blotting using mouse monoclonal antibodies to keratin proteins. Development and progression of MGD in the rabbit appears to correlate with increasing stratification and keratinization of the meibomian gland duct epithelium. In the early stages of MGD, focal areas of epithelial hyperkeratinization were identified by immunohistochemical staining using AE2 monoclonal antibody, specific for the 56.5 kD and 65-67 kD keratin protein marker for keratinized epidermis. As the severity of MGD progressed there was progressive increase in the AE2 staining of the duct epithelium. SDS-PAGE and immunoblotting of proteins from meibomian gland excreta in chronic MGD showed a progressive increase in both the 56.5 kD and 65-67 kD keratinization protein markers during development of MGD. We conclude that hyperkeratinization of the duct epithelium leading to plugging and dilation of the meibomian gland underlies the development of MGD following topical epinephrine treatment.

Animals↗

PubMed1989

Meibomian gland dysfunction. III. Meibomian gland lipids.

The lipid components of meibomian gland excreta were evaluated in rabbits after they received 2% topical epinephrine dropped into their eyes daily for a period of 6 months to a year to induce meibomian gland dysfunction (MGD). Changes were compared to excreta obtained from seven age-matched, untreated control rabbits. Comparison of the lipids from MGD lids with lipids obtained from control rabbits revealed, for clinically evident MGD, a marked increase in the lipids that are uniquely characteristic of epidermal tissue. These epidermal lipids are free sterols (large amounts) and a group of seven types of ceramides. The data are consistent with the hypothesis that the initiating factor of rabbit MGD is hyperkeratinization of the ductal epithelia. For clinically apparent MGD some hydrolysis of the sterol esters of the meibomian gland lipids also seems to have occurred. This was evidenced by the formation of an 8-fold increase in a cluster of anteiso fatty acids with chain lengths longer than C20 in the free fatty acid fraction. This group of free fatty acids was the same as the acids esterified to the sterol esters. We could detect no change in the lipid excreta obtained from rabbits that developed only subclinical MGD, consisting of orifice plugging and dilation of the duct.

Animals↗

PubMed1989

Dose-dependent effects of epidermal growth factor on corneal wound healing.

The dose-dependent effect of epidermal growth factor (EGF) on the development of wound tensile strength following full-thickness corneal wounds was evaluated in 60 adult rabbits. One eye from each rabbit received a single 7-mm long corneal incision. After injury each rabbit was treated three times daily for 5 or 10 days with either EGF at 0.001 mg/ml (10 eyes), 0.01 mg/ml (10 eyes), 0.1 mg/ml (10 eyes), 1.0 mg/ml (15 eyes), or vehicle (15 eyes). The tensile strength of the wound was evaluated using a 5-mm wide strip of cornea mounted on a tensiometer. We found that EGF at 0.1 mg/ml and at 0.01 mg/ml increased wound strength by 100% at 5 days and by 60% at 10 days (P less than 0.05 and P less than 0.05). However, EGF at 0.001 mg/ml and 1.0 mg/ml appeared to have no effect on wound strength. Histologic examination of full-thickness wounds in a separate series showed an increase in wound fibroblastic response and a diminished fibrin clot at 5 days in rabbits treated with 0.1 mg/ml and 0.01 mg/ml. We conclude that EGF enhances the wound strength of full-thickness corneal wounds in a dose-dependent manner which may be explained in part by an increased fibroblastic response. Concentrations of EGF greater or less than an optimal dose may be less effective in enhancing corneal wound strength.

Administration, Topical↗