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Biomedical subjects

A D Proia

Publications and source records attributed to A D Proia.

At least 37 records · Page 2Linked to original sources

Effect of protein kinase C inhibitors and activators on corneal re-epithelialization in the rat.

PURPOSE: To examine the ability of protein kinase C (PKC) inhibitors and activators to influence the rate of corneal re-epithelialization in the rat. METHOD: Rat corneas with 3 mm diameter central epithelial abrasions were organ-cultured in control medium or in medium with inhibitors or activators of PKC. RESULTS: In control corneas, the defect was completely re-epithelialized by 25 hr. In the presence of the PKC inhibitors staurosporine (100 nM), sphinganine (50 mumol/l), or H-7 (100 mumol/l) there were significantly larger epithelial defects than in controls after 5-25 hr of incubation. Re-epithelialization rates were similar to control corneas when the incubation medium contained HA1004 (100 mumol/l), an analogue of H-7 that is a potent inhibitor of cyclic adenosine monophosphate- and cyclic guanosine monophosphate-dependent protein kinases and a weak inhibitor of PKC. Two PKC activators, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12-myristate 13-acetate (PMA), were unable to enhance the rate of epithelial wound healing. CONCLUSIONS: Our results suggest that PKC activity is an important factor in regulating corneal epithelial wound healing, presumably by influencing cell migration. Moreover, the results with OAG and PMA suggest that PKC is maximally activated during re-epithelialization in this organ-culture assay.

Animals↗

Histopathological variation in keratoconus.

During examination of 131 penetrating keratoplasty specimens from patients with keratoconus obtained in an 11-year period, we observed two histopathologic variants based on the appearance of Bowman's layer and the corneal epithelium. "Typical" keratoconus specimens had multiple breaks in Bowman's layer and central epithelial thinning, whereas "atypical" corneas lacked breaks in Bowman's layer and had less thinning of the central epithelium. Ninety-five corneas were from patients who underwent grafting in only one eye. Seventy-six (80%) of these corneas were "typical" and 19 corneas (20%) were "atypical" in appearance. Both variants had similar degrees of central stromal thinning. Patients with "typical" and "atypical" corneas differed demographically by race only; 49% of "typical" and 95% of "atypical" corneas were from white individuals. Thirty-six corneas were from 18 patients who underwent bilateral penetrating keratoplasty. The histologic appearance of these corneal pairs was concordant in 13 patients and discordant (one "typical" and one "atypical" cornea) in five patients. Statistical analysis indicated that this distribution is not significantly different from that predicted by chance and suggests that "typical" and "atypical" corneas are manifestations of the same disease process.

Adolescent↗

Corneal argyrosis associated with silver soldering.

We report a patient who developed corneal argyrosis secondary to occupational silver soldering. Clinically, the cornea was notable for a green-brown discoloration localized to Descemet's membrane by slit-lamp biomicroscopy. Silver particles were identified within the anterior three eighths of Descemet's membrane by light and electron microscopy and energy-dispersive x-ray microanalysis. To our knowledge, the association between corneal argyrosis and silver soldering has not been previously reported.

Aged↗

Retrobulbar anesthesia and eyelid closure--effect on corneal angiogenesis.

We evaluated the effect of corneal anesthesia produced by retrobulbar injections of bupivicaine and epinephrine on corneal neovascularization in the rat. The eyelids were sutured closed to prevent dessication and ulceration of the insensitive corneas. The amount of corneal neovascularization induced in animals receiving a retrobulbar anesthetic did not differ from those receiving control solutions. However, rats receiving retrobulbar injections exhibited greater corneal neovascularization than those that did not. Rats that had their eyelids sutured or patched closed also had more neovascularization than animals that did not. Likewise, rats that had sutures placed in the upper and lower eyelids, without palpebral immobilization, manifested more neovascularization than rats without sutures. These studies suggest that corneal anesthesia does not affect neovascularization induced by silver/potassium nitrate cauterization and that retrobulbar injections and eyelid closure enhance corneal neovascularization.

Anesthesia, Local↗

The effect of total-body irradiation on corneal neovascularization in the Fischer 344 rat after chemical cauterization.

Previous investigations of corneal neovascularization after irradiation yielded discordant results. Most studies indicated that new blood vessel formation in the cornea is inhibited by irradiation. However, others reported that angiogenesis after corneal cauterization is similar in both irradiated and nonirradiated animals. To assess the effect of total-body irradiation on neovascularization further, the amount of angiogenesis was determined in irradiated rats after chemically induced corneal injury. Corneal tissue was evaluated quantitatively with computerized image analysis 2, 3, or 4 days postcautery in rats perfused with India ink and gelatin immediately after death. The rats were exposed to a single dose (9 Gy) of total-body irradiation 6 days before corneal cauterization. In both the nonirradiated and irradiated rats, neovascularization increased with the duration of the postcautery interval. The amount of corneal neovascularization was not significantly different in the irradiated and nonirradiated rats at any of the postcautery intervals studied. This investigation suggests that endothelial cell migration plays a more important role than cell replication in the pathogenesis of corneal angiogenesis in the Fischer 344 rat. Moreover, the suppression of corneal angiogenesis by irradiation may be dependent on the experimental conditions and species examined.

Animals↗

Histopathology of silicone oil keratopathy in humans.

Corneal endothelial decompensation is a frequent complication when silicone oil is used as a tamponade following vitrectomy for treatment of proliferative vitreoretinopathy in an aphakic eye. We evaluated the clinical, histopathological, and ultrastructural features of silicone oil-induced keratopathy in 10 patients who developed corneal complications requiring penetrating keratoplasty. Clinically, some cases showed corneal edema, corneal hypesthesia, endothelial opacification, band keratopathy, and peripheral corneal vascularization. Histopathologically, retrocorneal membranes were present, and different degrees of stromal hypercellularity, superficial stromal calcification, and vascularization were noted. The ultrastructural features of endothelial cell loss and retrocorneal membrane formation are consistent with changes previously reported in rabbits and cats receiving intracameral silicone oil injections.

Adult↗

12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid is a more potent neutrophil chemoattractant than the 12(R) epimer in the rat cornea.

12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE] is reported to be more potent than its epimer 12(S)-HETE as a chemoattractant for human neutrophils in vitro and following topical application to the skin. To assess the in vivo neutrophil chemoattractant potencies of 12(S)-HETE and 12(R)-HETE in the rat, we injected 1 microgram, 5 micrograms, or 10 micrograms of these eicosanoids into the corneal stroma. Rats were killed 12-15 hours after injection, and the number of neutrophils in the stroma was counted in a histological section of the cornea including the injection site. The number of neutrophils was significantly increased in corneas injected with 5 micrograms (+103% of control) or 10 micrograms (+456% of control) of 12(S)-HETE and in those injected with 10 micrograms of 12(R)-HETE (+111% of control). The neutrophilic infiltrate in corneas injected with 1 microgram or 5 micrograms of 12(S)-HETE was not significantly different from that in corneas injected with 1 microgram of leukotriene B4. The data for the 10 micrograms injections indicate that 12(S)-HETE is a more potent neutrophil chemoattractant than 12(R)-HETE in the rat cornea. Our results suggest that species or tissue specificity may determine the relative potencies of 12-HETE epimers as chemoattractants for neutrophils, and that 12(S)-HETE may be an important inflammatory mediator in the rat cornea.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

The effect of oxygen on corneal neovascularization.

Since tissue oxygen levels are believed to play a pivotal role in new vessel growth in several situations, we studied the effect of several oxygen concentrations (0, 10, 21, 50, 75, or 100%) on corneal vascularization induced in the rat by chemical cautery. We achieved this by perfusing known concentrations of oxygen through goggles fitted over both eyes of the rat after corneal cauterization. Neovascularization was measured in flat corneal preparations with India ink-filled vessels 4 days postcautery using computerized image analysis. The angiogenic response of rats whose eyes were continuously exposed to 0-75% oxygen were not significantly different from each other. The mean response in corneas exposed to 100% oxygen was 10-21% lower than all of the other groups, and this difference was statistically significant when compared to oxygen concentrations of 0, 21 and 75%. The reason for the inhibitory effect of 100% oxygen remains to be determined, but it may represent a toxic effect of oxygen free radicals on the vascular endothelium.

Animals↗

The effects of total lymphoid irradiation upon corneal vascularization in the rat following chemical cautery.

The effect of total lymphoid irradiation (TLI), a form of radiotherapy known to suppress the number of circulating lymphocytes, on corneal neovascularization was assessed in rats. The corneas of TLI-treated rats were cauterized with silver/potassium nitrate one day after delivering gamma irradiation in five equal fractions (10 Gy total dose). Corneal neovascularization was assessed quantitatively by computerized image analysis in corneal flat preparations 4 days after corneal injury following perfusion of the circulation with India ink. TLI reduced the total leukocyte, lymphocyte, neutrophil, and platelet counts below preirradiation levels. The number of circulating lymphocytes was reduced more than neutrophils and platelets. TLI caused a predominance of cytotoxic/suppressor lymphocytes. Tissue examinations 4 days after TLI disclosed an absence of the thymus, as well as a markedly reduced number and size of lymph nodes. TLI rats had less corneal vascularization than nonirradiated controls. Our findings are consistent with the hypothesis that leukocytes play an important role in the pathogenesis of corneal angiogenesis following chemical cautery, but this study does not indicate how TLI suppresses corneal neovascularization.

Animals↗

Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat.

We used computerized image analysis to evaluate quantitatively the ability of topically applied corticosteroids (dexamethasone sodium phosphate, prednisolone acetate), cyclooxygenase inhibitors (flurbiprofen, indomethacin, ketorolac), lipoxygenase inhibitors (REV 5901, esculetin, quercetin), and dual cyclooxygenase/lipoxygenase inhibitors (BW 755C, BW A540C) to reduce corneal neovascularization in the rat induced by silver/potassium nitrate cauterization. Significant decreases in the neovascular response were found with corticosteroids and cyclooxygenase inhibitors. A complete dose-response curve was performed for a representative compound from each class. Dexamethasone was found to be superior to flurbiprofen in its ability to reduce neovascularization in this model, while no significant inhibition was noted with either REV 5901 or BW 755C, even at high doses. We conclude that the corneal angiogenic response in this model can be reduced by inhibition of cyclooxygenase as well as by other mechanisms that are steroid-dependent but are, as yet, poorly defined.

Administration, Topical↗

Primary orbital leiomyosarcoma. A case report and review of the literature.

An 82-year-old woman presented with a five-week history of painless proptosis. Results of clinical evaluation, including computed tomography, were consistent with a benign orbital tumor. Biopsy followed by surgical resection disclosed leiomyosarcoma. We reviewed the literature and studied the clinical spectrum of this rare disease of the orbit.

Aged↗

Retinal toxicity of cyanoacrylate tissue adhesive in the rabbit.

N-butyl-2-cyanoacrylate tissue adhesive was injected into the preretinal space of rabbit eyes to study potential toxicity to the retina. Application of 3.3-10.0 ul of cyanoacrylate tissue adhesive showed localized but definite retinal toxicity. White halos appeared surrounding the preretinal cyanoacrylate immediately after injection with a gradual evolution of the white areas into pigmentary scars by 1 month. Histological examination confirmed severe focal necrosis of the retina. No identifiable distant toxic effects or electrophysiologic changes were observed during the 6-month follow-up period.

Animals↗

Quantitation of corneal neovascularization using computerized image analysis.

We have developed a method for quantitating corneal neovascularization, induced in anesthetized rats by silver nitrate/potassium nitrate cauterization, using a LeMont OASYS video input image analyzer. Corneal vessels are visualized by perfusing the upper half of deeply anesthetized animals with a mixture of 10% india ink, 11% gelatin in lactated Ringer's solution. The eyes are then rapidly cooled using a stream of compressed dichlorodifluoromethane (Freon) to solidify the gelatin mixture. Magnified images of flat preparations of the corneas are acquired using a television camera attached to a dissecting microscope. The images are electronically converted to digital form and the digitized data are stored in the image analyzer. The area of the cornea and blood vessels are independently determined by analyzing the digitized data as discrete values of varying shades of gray (gray-scale analysis). The area and gray scale of the injury and its distance from the corneoscleral limbus can also be measured to determine variability of location and intensity of the injury in different animals. This technique allows the area occupied by new blood vessels during studies on corneal neovascularization in rats to be rapidly quantitated.

Animals↗

Intraocular pressure following intravitreal silicone oil injection.

The clinical features of 100 consecutive cases and the histopathology of six enucleated eyes, all having undergone silicone oil injection for complicated retinal detachments, were studied with regard to the incidence and mechanisms of postoperative intraocular pressure changes. Preoperatively, five patients had glaucoma and 35 had hypotony (7 mm Hg or less). Immediately after surgery, 43 patients had glaucoma and 14 had hypotony, while seven had glaucoma and 39 had hypotony in the late postoperative period (average follow-up of 1 year). In most cases, the mechanism of intraocular pressure change did not appear to be directly related to the presence of silicone, but rather to the preoperative status of the eye and other aspects of the vitreoretinal surgery. When silicone was a factor, the resulting intraocular pressure appeared to represent a balance between mechanisms obstructing aqueous outflow (pupillary block and the reaction to silicone bubbles in the anterior chamber angle) and mechanisms reducing aqueous production (cyclitic membranes and retinal detachment).

Adolescent↗

Histopathologic and immunochemical features of lattice corneal dystrophy type III.

We examined seven corneas from five patients with a new form of lattice corneal dystrophy (designated lattice corneal dystrophy type III) by light and electron microscopy. Numerous amyloid deposits were scattered throughout the corneal stroma, some of which were much larger than those usually observed in either lattice corneal dystrophy type I or II; these were located predominantly midway between the epithelium and the endothelium. Image analysis disclosed that the cross-sectional size of the large stromal amyloid deposits was significantly greater than those in age-matched patients with lattice corneal dystrophy type I. All patients had a discontinuous band of amyloid (15 to 25 micron wide) in the superficial stroma beneath Bowman's layer, which usually had only one or two small disruptions. Descemet's membrane and the endothelium were normal. The stromal deposits, which were composed of 10-nm diameter fibrils typical of amyloid, stained positively with Congo red after the histologic sections were pretreated with dilute potassium permanganate. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissue indicated that only some deposits reacted weakly with antibodies to amyloid protein AA. The deposits stained positively with antibodies to protein AP and negatively with antibodies to kappa and lambda immunoglobulin light chains.

Amyloid↗

Experimental transvitreal cyanoacrylate retinopexy in a primate model.

We evaluated the use of transvitreal cyanoacrylate retinopexy in the treatment of experimental rhegmatogenous retinal detachment during vitreous surgery in the cynomolgus monkey. The chorioretinal adhesions produced with cyanoacrylate tissue adhesive as compared with those produced by transscleral retinal cryopexy were more rapid in onset as well as stronger. To test the efficacy of cyanoacrylate retinopexy further, a 360-degree peripheral retinectomy was created in five eyes with circumferential cyanoacrylate application to the posterior retinal edge. The cyanoacrylate retinopexy did not prevent the development of proliferative vitreoretinopathy with traction retinal detachment, but in three of the eyes the tissue adhesive continued to maintain retinal apposition to the retinal pigment epithelium at the retinotomy edge. Histologic examination of the retinas disclosed a foreign body reaction adjacent to the cyanoacrylate sites, but there was no evidence of any distant effects caused by the tissue adhesive.

Animals↗