Biomedical subjects

K R Kenyon

Publications and source records attributed to K R Kenyon.

At least 55 records · Page 3Linked to original sources

PubMed1991

Effect of fibronectin on corneal epithelial wound healing in the vitamin A-deficient rat.

The authors investigated the in vitro and in vivo effects of fibronectin (Fn) on the migration of corneal epithelium of vitamin A-deficient (A-) and pair-fed control (A+) rats. Groups treated with 50 micrograms/ml Fn showed accelerated healing of epithelium in vitro (P less than 0.05) compared with control groups of A- and A+ rats. However, when 100 micrograms/ml Fn eye drops were administered 14 times over 20 hr, they had no significant effect on A+ rats in vivo, but increased the healing in A- rats (P less than 0.05). In this model, Fn promoted the healing of corneal epithelium under A- conditions where decreased endogenous Fn is seen, whereas A+ corneas in vivo, which have sufficient Fn over the wound surface, did not benefit from topical Fn administration.

Administration, Topical↗

PubMed1990

Alteration of epithelial paracellular permeability during corneal epithelial wound healing.

We studied the paracellular permeability to mannitol of corneas with epithelium of corneal, limbal, or conjunctival origin. Corneas with epithelial defects reepithelialized by corneal or limbal epithelium were nonvascularized; the corneal permeability was initially increased and returned to normal 3 days later. When epithelial defects extended beyond the limbus, they were healed by conjunctival epithelium. If corneas remained avascular or minimally vascularized, the conjunctiva-derived epithelium underwent a transdifferentiation process into a cornealike morphology in which the corneal permeability was initially increased upon complete reepithelialization, and gradually decreased to a level similar to that of normal cornea, 4 weeks after healing. However, when corneas became vascularized, the conjunctiva-derived epithelium retained its original phenotype, and corneal permeability remained increased throughout the 8-month period of study. The deranged barrier functions noted in the above vascularized cornea were demonstrated further by horseradish peroxidase tracer, which was found in the intercellular spaces of conjunctiva-derived epithelium of vascularized corneas but not in the avascular corneas with epithelia of corneal or limbal origin, or transdifferentiated conjunctival epithelium. To study further the effect of subsequent ocular surface trauma, conjunctival biopsy was performed on transdifferentiated avascular corneas 3 months after initial wounding. The biopsy resulted in extensive vascularization in three of eight previously nonvascularized corneas. Two weeks later, the corneal permeability was increased to a level similar to that of conjunctiva. These results indicate that corneal epithelial paracellular permeability correlates well with the status of the epithelial phenotype.

Animals↗

PubMed1990

Corneal surface irregularities and episodic pain in a patient with mucolipidosis IV.

Mucolipidosis IV is a lysosomal storage disease characterized by prominent involvement of the corneal epithelium. A 5-year-old boy with mucolipidosis IV experienced recurrent episodes of severe ocular pain, tearing, and ipsilateral facial flushing. This was suggestive of reflex sympathetic dystrophy, a syndrome of pain and sympathetic hyperactivity. The examination revealed marked corneal surface irregularities, corresponding to massive accumulations of intracytoplasmic storage material in the epithelium. Episodic pain in patients with mucolipidosis IV is an important symptom, presumably reflecting the distinctive corneal ultrastructural abnormality in this disease.

Cataract Extraction↗

PubMed1990

Immunocytochemical localization of gentamicin in the rabbit retina following intravitreal injection.

The localization of gentamicin in the retina after a single intravitreal injection in the rabbit eye was examined by indirect immunofluorescent staining with goat antigentamicin antiserum. Eight hours after the injection of 400 micrograms of gentamicin, staining was observed in the ganglion cell layer, the inner plexiform layer, the inner nuclear layer, and the photoreceptors. By 12 hours, the staining was also observed in the retinal pigment epithelium. Howeever, by 24 hours the staining was predominantly found in the retinal pigment epithelium and choriocapillaris, and only occasional staining was seen scattered in the neurosensory retina. At 36 to 48 hours, the labeling was confined to the retinal pigment epithelium and choriocapillaris. Electron microscopy confirmed the cytoplasmic localization of gentamicin in the retina.

Animals↗

PubMed1990

Time course of experimental Pseudomonas aeruginosa keratitis in contact lens overwear.

New perfilcon contact lenses (71% water) were placed on one eye of 36 rabbits under complete tarsorrhaphy for 7 days. The lenses were then removed, and 18 were incubated for 1 hour with a suspension of 1 x 10(8) colony-forming units per milliliter of Pseudomonas aeruginosa and replaced on their respective corneas. The remaining 18 eyes were inoculated with 0.1 mL of the P aeruginosa suspension; the lenses were not replaced. All eyes were again closed by tarsorrhaphy for 4, 8, 16, 24, 36 , or 48 hours. Ulcerative keratitis occurred in contact lens-wearing eyes only, as P aeruginosa penetrated the epithelium at 8 to 36 hours, and polymorphonuclear leukocyte migration began at 24 hours. Compared with conventional abrasion-wound models, the time course of infectious keratitis in this model was delayed, possibly due to less preexisting corneal trauma, but our findings suggest that soft contact lens wear facilitates bacterial invasion and also inhibits the host inflammatory response.

Animals↗

PubMed1990

Experimental Pseudomonas aeruginosa keratitis from extended wear of soft contact lenses.

We used a rabbit model to investigate the pathogenesis of soft contact lens-induced bacterial keratitis. Rabbit eyes underwent complete tarsorrhaphy for 7 days either with (group A, n = 14) or without (group B, n = 13) new sterile soft contact lenses. On day 7, an increase in mean corneal thickness (20.3% in group A and 17.2% in group B) was detected. New or rabbit-worn soft contact lenses were then inoculated with 10(7) colony-forming units of Pseudomonas aeruginosa or by 0.1 mL of P aeruginosa suspension. On day 9, conjunctival cultures of all eyes yielded P aeruginosa. Corneal infection developed in 11 of 14 eyes wearing new or worn, contaminated soft contact lenses. Bacterial keratitis did not develop in any of the 13 eyes inoculated with P aeruginosa suspension. Light and electron microscopy of infected eyes showed abundant polymorphonuclear neutrophils destroying the epithelium, basement membrane, and stroma. Few bacteria could be detected and only in the deep stroma. Since bacterial suspension alone caused no inflammation, soft contact lens-wear appears crucial to corneal infection in this model.

Animals↗

PubMed1990

Intraocular penetration of rifampin after oral administration.

Rifampin, the most potent anti-staphylococcal drug known, was examined for its penetration into the aqueous and vitreous of rabbits after a single oral dose of 150 mg, 300 mg, or 600 mg. Maximum levels after the 150 mg dose were achieved at 4 h and were 4.2 micrograms/ml in the aqueous and 2.2 micrograms/ml in the vitreous. After the 300 mg dose, maximum levels were also achieved at 4 h, and were 5.0 micrograms/ml in the aqueous and 2.6 micrograms/ml in the vitreous. The 600 mg dose produced maximum levels at 6 h after administration, with 20.0 micrograms/ml in the aqueous and 15.2 micrograms/ml in the vitreous. These levels exceed the minimum inhibitory concentration for many microorganisms and suggest additional investigation into possible applications of systemic rifampin in the prophylaxis and treatment of bacterial endophthalmitis.

Administration, Oral↗

PubMed1990

Metabolic analysis of reepithelializing rabbit cornea using phosphorus-31 nuclear magnetic resonance spectroscopy.

To investigate metabolic differences between the central and peripheral cornea the latter including the limbal area, corneas were dissected and examined using phosphorus-31 (31P) nuclear magnetic resonance spectroscopy. Since most 31P signals originate from the epithelium, 31P spectra of the cornea primarily represent the metabolic state of the epithelium. The spectra of the peripheral cornea showed all phosphorus resonances detected in the whole cornea; in contrast, the central cornea showed no phosphocreatine and glycerophosrylethanolamine, and only low levels of ATP. These results indicate that there is a higher metabolic activity in the peripheral epithelium, especially in the limbal area, than in the central epithelium. To evaluate the metabolic state of corneal epithelium during regeneration, we also examined corneas reepithelializing after 7 mm of central epithelial tissue had been removed by mechanical scraping. Rabbits were killed 24 and 48 h after scraping. The reepithelializing corneas clearly showed an increase in ATP, phosphocreatine, and sugar phosphates with time, although phosphorylcholine remained depressed. These findings suggest that the reepithelializing cornea has an elevated level of energy production and that it may have reached a higher steady state, thereby indicating accelerated metabolism of the epithelium during regeneration.

Animals↗

PubMed1990

Effects of altering the eicosanoid precursor pool on neovascularization and inflammation in the alkali-burned rabbit cornea.

The effects of altering the eicosanoid precursor pool on several aspects of the nonimmunologically mediated inflammatory and angiogenic processes that follow 1N and 4N NaOH alkali burning of the rabbit cornea were compared with controls. Diets were supplemented with several dosages of oils containing either gamma-linolenic acid (GLA) (borage oil), eicosapentaenoic acid (EPA) (sardine oil), or a combination of the two in a dose-response protocol. Significant changes in serum fatty acid composition were demonstrated. Gamma-linolenic acid proved consistently superior to EPA in modulating the neovascular response judged by three neovascular indices. At 14 days, GLA significantly reduced the polymorphonuclear leukocyte and macrophage inflammatory infiltrate and EPA reduced the macrophage component, both with high dose; EPA also reduced keratocyte proliferation. Wound-healing parameters were unaffected. Evidence for GLA-EPA synergism was modest. Prolonged neovascular responses and chronic inflammation occurring in the clinically relevant context of severe structural damage can be modulated by nutritional alteration of the eicosanoid precursor pool.

Animals↗

PubMed1990

Stromal degradation in vitamin A-deficient rat cornea. Comparison of epithelial abrasion and stromal incision.

Epithelial abrasions (3-mm diameter) and linear stromal incisions (50-75% depth) were made in vitamin A-deficient (A-) rat corneas to investigate what are contributory factors to the development of keratomalacia. Sixty-four rats were killed at various times after injury, and the corneas were histologically examined. In pair-fed control corneas, wounds healed without stromal degradation. Although abraded A- corneas were infiltrated by numerous polymorphonuclear neutrophil leukocytes (PMNs), reepithelialization eventually occurred and severe stromal degradation was not evident, suggesting that PMN infiltration alone cannot cause keratomalacia. In incised A- corneas, six (20%) exhibited marked stromal degradation, of which three (10%) were infected. Two other corneas studied shortly after incision were in the initial stages of infection. The results suggest that stromal injury importantly contributes to the development of keratomalacia. Bacterial infection might also be contributory. Cytochrome oxidase staining showed that metabolic functional levels of incised A- corneas were accelerated only in the wound zone, whereas abraded A- corneas were metabolically accelerated throughout.

Animals↗

PubMed1990

Pathologic changes in the exorbital lacrimal gland of the vitamin A-deficient rat.

Histologic changes in lacrimal glands of vitamin A-deficient (A-) and pair-fed control rats were compared. In A- lacrimal glands, secretory granules were strikingly diminished, and rough endoplasmic reticulum appeared somewhat atrophic. Nuclei of acinar cells were hyperchromatic and pleomorphic. Using alcian blue-PAS, no positive staining was present in acini of A- lacrimal glands, whereas in controls apical portions of acini were intensely stained. Thus, lacrimal tissues of A- rats were thought to be poorly differentiated as a glandular epithelium. When A- rats were supplemented with retinyl acetate, secretory granules reappeared, rough endoplasmic reticulum cisternae greatly dilated, and mitochondria proliferated, indicating accelerated secretory activity. Resupply of vitamin A can induce glandular differentiation in A- lacrimal tissues. Tear volume was not decreased in A- rats compared with pair-fed controls. Regression of secretory organelles in A- lacrimal tissues may lead to a decrease in protein and mucoprotein secretion and subsequent changes in tear composition.

Animals↗

PubMed1990

Endothelial specular microscopy in children with retrolental fibroplasia undergoing open-sky vitrectomy.

Thirty-three patients aged 4 to 63 months with extensive retinal detachment due to cicatricial retrolental fibroplasia (RLF) and two non-RLF patients aged 26 and 81 months with normal corneas underwent specular microscopy and ultrasonic pachymetry during examination under anesthesia. Thirty-six eyes of preoperative RLF patients without anterior synechiae and 4 eyes of the two non-RLF patients had high endothelial cell density (ECD) of 5,105 +/- 790.4/mm2 (mean +/- SD) and 4,377 +/- 141.7/mm2, respectively, and increased corneal thickness. The ECD value showed significant negative correlation with vertical corneal diameter (P less than 0.005), but not with age. The ECD values, corrected to average adult corneal size, were 3,900 +/- 550/mm2, which were close to values extrapolated from adult ECD data. The average cell loss for 10 eyes undergoing specular microscopy before and after open-sky vitrectomy was 15%, but 8 of these eyes showed an unchanged ECD ratio of 0.79-1.3 between the two measurements. Furthermore, 17 eyes which were examined only postoperatively also showed a high average ECD of 4,175 +/- 1,012/mm2.

Cell Count↗

PubMed1990

Histopathology of human keratorefractive lenticules.

Eight human corneal lenticules (three from keratophakia, two from hypermetropic keratomileusis, and three from myopic keratomileusis) were examined by light and electron microscopy. The keratophakic lenticules were removed for optical reasons 3, 3.5, and 6 months after surgery. Microscopically, all displayed hypocellularity, mature collagen fibrils and microfibrils, keratocyte ghosts, and keratocytic debris. The hypermetropic keratomileusis specimens were removed at 13 and 14 months postoperatively, the first because of opacities from enzymatic digestion of the cornea, and the second due to contact lens-induced erosion of Bowman's layer and decreased lacrimal secretion. Ultrastructurally, both lenticules exhibited fractures in Bowman's layer, and the 14-month specimen showed multilayered squamous epithelia. The myopic keratomileusis specimens were removed at 4, 8, and 48 months postoperatively due to opacification of the interface caused by delayed epithelial healing, detergent trauma, and previous epithelization, respectively. Electron microscopy revealed fractures in Bowman's layer, subepithelial fibrocellular growth, sparse keratocyte populations of the anterior stroma, porous collagen bundles, keratocytic debris, and regions of epithelial ingrowth.

Adult↗

PubMed1990

In vitro toxicity of gentamicin to corneal epithelial cells.

We report morphologic and viability changes in the rabbit corneal epithelium exposed in vitro to gentamicin sulfate. Rabbit corneal epithelial cells (3 x 10(5)) were seeded in replicate 24-well plates at their first in vitro passage, and gentamicin in concentrations of 0, 50, 250, 500, 1,000, or 5,000 micrograms/ml was added to the tissue culture medium beginning 7 days after subculture. By phase contrast microscopy, changes in cell morphologic appearance, particularly increased cytoplasmic granularity, were observed in the 5,000-micrograms/ml groups as early as 24 h after introduction of the drug. At 48 h, similar findings were observed in the 250-micrograms/ml group and at all higher concentrations. The cytoplasmic granularity was not noted in the 0- or 50-micrograms/ml groups. By electron microscopy, these observations correlated with ultrastructural findings of increased accumulations of intralysosomal bodies beginning in the 250-micrograms/ml group after 48 h of exposure to gentamicin. Furthermore, a statistically significant difference (p = 0.001) was demonstrated between the total number of viable cells in the low-dose group (50-micrograms/ml) and the high-dose groups (greater than or equal to 250-micrograms/ml) for exposure periods of 48 h or more. These findings demonstrate aminoglycoside toxicity to corneal epithelial cells in vitro similar to that seen in the human kidney and conjunctiva.

Animals↗

PubMed1989

The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group.

Over 13 million people in the United States wear soft contact lenses for refractive correction. Ulcerative keratitis is considered the most serious adverse effect of the use of contact lenses. We performed a case-control study with 86 cases patients, estimating separately for hospital-based (n = 61) and population-based (n = 410) controls the relative risk of ulcerative keratitis among users of extended-wear as compared with daily-wear soft contact lenses. The relative risk of ulcerative keratitis for extended-wear as compared with daily-wear lenses among the population-based controls was 3.90 (95 percent confidence interval, 2.35 to 6.48) and among the hospital-based controls, 4.21 (95 percent confidence interval, 1.95 to 9.08). Thirty-eight percent of those with extended-wear lenses used them only during the day, and 11 percent of those with daily-wear lenses occasionally wore them overnight. When lens wearers were distinguished according to their overnight use of lenses, the users of extended-wear lenses who wore them overnight had a risk 10 to 15 times as great as the users of daily-wear lenses who did not, and the users of daily-wear lenses who sometimes wore them overnight had 9 times the risk of the users of such lenses who did not. For the users of extended-wear lenses, the risk of ulcerative keratitis was incrementally related to the extent of overnight wear. A reduction in risk associated with more frequent attention to lens hygiene was almost significant. We conclude that soft contact lenses worn overnight carry a significantly greater risk for ulcerative keratitis than soft lenses worn only during the day.

Contact Lenses, Extended-Wear↗

PubMed1989

The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses.

The wearing of contact lenses has increased dramatically in the past decade; over 4 million people in the United States now use extended-wear soft contact lenses, and 9 million use daily-wear soft contact lenses. Numerous reports have caused concern that the use of soft contact lenses, especially extended-wear lenses, may result in a substantial risk of ulcerative keratitis. To examine this issue, we conducted a prospective study in five New England states to estimate the incidence of ulcerative keratitis among those who use cosmetic extended-wear and daily-wear soft contact lenses. To obtain the numerator for each estimate of incidence, we surveyed all practicing ophthalmologists in the study area to identify all new cases diagnosed over a four-month period. To provide the denominator, we conducted a survey of 4178 households to estimate the number of persons who wore each type of soft contact lens. The annualized incidence of ulcerative keratitis was estimated to be 20.9 per 10,000 persons using extended-wear soft contact lenses for cosmetic purposes and 4.1 per 10,000 persons using daily-wear soft contact lenses for cosmetic purposes (P less than 0.00001).

Adolescent↗

PubMed1989

Gentamicin toxicity in the primate retina.

To study the toxic effect of aminoglycoside antibiotics in the primate retina, gentamicin sulfate was injected into the center of the vitreous cavity of Cebus navrigatus monkeys. At a dose of 1000 to 3000 microgram, a picture consistent with apparent macular infarction appeared on fundus examination and fluorescein angiography by three days and gradually faded by 21 days. While light and electron microscopic examination of the retina showed no primary vascular lesions, striking damage to the inner retinal layers, mainly the nerve fiber layer, ganglion cell layer, and the inner plexiform and nuclear layer, was seen. Less severe effects in the outer retinal layers and the retinal pigment epithelium occurred. These observations suggest that the neurotoxic effect of intravitreal gentamicin was sufficient to cause a complete shutdown of the regional blood flow, perhaps by the mechanism of granulocytic plugging of the capillary bed. Although this toxic effect occurred at doses considerably in excess of what has been recommended for clinical use in humans, the "safe" dose of intravitreal gentamicin, nevertheless, remains to be established unequivocally.

Animals↗

PubMed1989

Fibronectin and corneal epithelial wound healing in the vitamin A-deficient rat.

The time course of the appearance of fibronectin (Fn) on wounded corneal surfaces was studied in vitamin A-deficient (A-) and pair-fed control rats. At various times following a central epithelial abrasion, the tissue was harvested, and Fn was localized on frozen corneal sections by an indirect immunofluorescence technique. There was no detectable Fn in intact, nonwounded control or intact A-corneas, except for Descemet's membrane. Within a half hour after abrasion, a band of Fn appeared on the denuded corneal surface of pair-fed control rats and became a continuous, prominent layer at four hours. This layer remained until 16 hours but disappeared at 24 hours when the epithelium had resurfaced over the defect. In severely A- rats, reepithelialization following central epithelial abrasion was delayed, and no Fn band was discernible at any time from one to 32 hours after injury. Light microscopy revealed a progressive increase in polymorphonuclear neutrophil infiltration with time in the underlying stroma in severely A- rats. This study indicated that in severe vitamin A deficiency, delayed epithelial migration is associated with an inflammatory cell layer and occurred in the absence of Fn.

Animals↗