Cornea and sclera.
TL;DR: Experimental animals have been used and similarities between experimentally induced herpetic keratitis in the rabbit and the naturally occurring disease in man are evident, providing evidence that the rabbit eye is the closest to an ideal model eye for studies on the natural history ofHerpesvirus hominis.
Abstract: cornea warrant periodic critical analysis, few others have caused more controversy than the various virulent viruses and their effect on this tissue. Herpesvirus hominis (herpes simplex virus, HSV) infection is by far the most important viral disease of the eye in the Western hemisphere and will be discussed in detail. Mechanisms of disease and means of therapy are both subject to dispute and hopefully will be brought into perspective by this effort. Additionally, other viruses and the Chlamydiae group will be mentioned. In order to understand better the patho¬ genesis of ocular herpesvirus hominis infec¬ tion, experimental animals have been used, particularly the rabbit. Numerous similari¬ ties are now evident between experimentally induced herpetic keratitis in the rabbit and the naturally occurring disease in man. In both species, dendritic lesions, corneal anes¬ thesia, favorable response to antimetabolite drugs, deleterious effects to corticosteroids, and disciform keratitis may occur. Also, cir¬ culating antibodies are formed and remain along with the persistence of virus and recurrences of infection with or without ker¬ atitis. These similarities provide evidence that the rabbit eye is the closest to an ideal model eye we have for studies on the natural history of herpetic keratitis and for in¬ vestigation of latency in herpetic infection.'
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TL;DR: Pseudomonas aeruginosa is an ubiquitous pathogen capable of infecting virtually all tissues as discussed by the authors, and a large variety of virulence factors contribute to its importance in burn wounds, lung infection and eye infection.
1,342 citations
TL;DR: The detection of LR-RNAs suggests the possibility that these RNAs or their products may play significant roles in the initiation and/or maintenance of HSV-1 latency.
Abstract: Using a combination of in situ hybridization and Northern (RNA) blot analysis, we investigated herpes simplex virus type 1 (HSV-1) transcriptional activity in an ocular rabbit model of HSV-1 latency. Radioactively labeled cloned fragments, representing virtually the entire HSV-1 genome, were individually hybridized to RNA in sections of trigeminal ganglia taken from rabbits during the latent phase of infection with HSV-1 (McKrae). Our results suggest that two discrete latency-related RNAs (LR-RNAs) may be present. The LR-RNAs were localized mainly in the nuclei of neurons. The more abundant LR-RNA was detected in approximately 3% of all neurons examined and was designated major LR-RNA. The other LR-RNA, designated minor LR-RNA, was detected in approximately 0.3% of neurons from latently infected rabbits. The genes for the LR-RNAs mapped in the vicinity of the immediate-early gene ICP0 (also designated IE110). The gene for the major LR-RNA partially overlapped the left (3') end of the ICP0 gene. In situ hybridization with single-stranded RNA probes showed that this LR-RNA was of complementary sense to that of ICP0 mRNA. Northern blot analysis gave an approximate size for this LR-RNA of 1.8 to 2.2 kilobases. The minor LR-RNA mapped to or near the right (5') end of the ICP0 gene. The detection of LR-RNAs suggests the possibility that these RNAs or their products may play significant roles in the initiation and/or maintenance of HSV-1 latency.
369 citations
TL;DR: The pattern of inhibition for all three enzymes suggests that isomers 6A and 6B is the (R,S) compound, stereochemically analogous to the L,L-dipeptide, and isomer 6B are the (S,S).
Abstract: The hydroxamic acid HONHCOCH2CH(i-Bu)CO-L-Trp-NHMe, isomer 6A (GM 6001), inhibits human skin fibroblast collagenase with Ki of 0.4 nM using the synthetic thiol ester substrate Ac-Pro-Leu-Gly-SCH(i-Bu)CO-Leu-Gly-OEt at pH 6.5. The other isomer, 6B, which has the opposite configuration at the CH2CH(i-Bu)CO alpha-carbon atom, has a Ki of 200 nM for this enzyme. GM 6001 is one of the most potent inhibitors of human skin fibroblast collagenase yet reported. GM 6001 has a Ki of 20 nM against thermolysin and Pseudomonas aeruginosa elastase. Isomer 6B has a Ki of 7 nM against thermolysin and 2 nM against the elastase. 6A and 6B are the most potent hydroxamate inhibitors reported for these bacterial enzymes. The pattern of inhibition for all three enzymes suggests that isomer 6A is the (R,S) compound, stereochemically analogous to the L,L-dipeptide, and isomer 6B is the (S,S) compound, analogous to the DL-dipeptide. The tolerance of the D configuration by thermolysin and the elastase allows these inhibitors to discriminate between the human and bacterial enzymes simply by inversion of configuration at the CH2CH(i-Bu)CO alpha-carbon atom. Substitution of the potential metal liganding groups carboxylate and hydrazide for the hydroxamate group yields much weaker inhibitors for all three enzymes.
281 citations
TL;DR: A review of the contribution of various types of light microscopy, electron microscopy and atomic force microscopy to the understanding of the distribution and organization of collagen types within the corneal and scleral stroma from a microscopical perspective is presented in this paper.
225 citations
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TL;DR: This review will concentrate on re¬ search in the past two decades and is limited, in the main, to English lan¬ guage sources.
Abstract: cesses affecting the cornea. Diagnosis and treatment of corneal disease de¬ mand an understanding of the events occurring in the reparative processes in the cornea. Widespread clinical interest has engendered intense re¬ search activity, and the resultant lit¬ erature is voluminous. The appli¬ cation of the techniques of electron microscopy, in particular, has given considerable aid to our understanding of corneal healing. This review will concentrate on re¬ search in the past two decades and is limited, in the main, to English lan¬ guage sources. The interest in corneal wound heal¬ ing extends back well into the 19th century. Early studies described basic events in corneal wound healing in excellent detail. A subsequent lull in research in this subject is evident un¬ til the 1940s, when a series of fine papers extending our knowledge ap¬ peared; many of these studies were the result of World War II research directed to the effects of noxious agents on the cornea. Periodic studies appeared in the 1950s describing ex¬ perimental histological and histochemical findings; application of the techniques of electron microscopy in the 1960s has added a new dimension
188 citations
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TL;DR: A collagenase, operative at neutral and alkaline pH, has been extracted from the granule fraction of human granulocytic leukocytes and it digests reconstituted collagen fibrils and reduces the viscosity of collagen solutions.
Abstract: A collagenase, operative at neutral and alkaline pH, has been extracted from the granule fraction of human granulocytic leukocytes. It digests reconstituted collagen fibrils and reduces the viscosity of collagen solutions. Cleavage of collagen in solution with purified enzyme produces the discrete products characteristic of other animal collagenases.
311 citations
Journal Article•
TL;DR: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma that lead to sensitization of the recipient and to graft rejection when appropriate vascularization is induced.
Abstract: Techniques have been developed for the transplantation of allografts of pure rabbit corneal epithelium and of endothelium with Descemet's membrane and only minimal amounts of adherent donor stroma. By appropriately inducing vascularization of the donor graft, the recipient becomes sensitized to and ultimately rejects the pure epithelial graft. The epithelium is rejected as a moving front of infiltrated and dying donor cells, with the rapidly regenerating recipient epithelium effecting immediate repair of the defect. The entire epithelial rejection process takes place in the absence of persisting stromal edema and cloudiness. Sensitization by, and rejection of, pure corneal stromal allografts were also studied. Rejection is characterized by a diffuse band of leukocytic infiltrate which sweeps across the donor tissue, leaving dead keratocytes in its wake. Endothelial allografts also lead to sensitization of the recipient and to graft rejection, again when appropriate vascularization is induced. Like epithelium, the rejection of corneal endothelium is associated with an advancing front of densely infiltrated and dying cells. In this instance, however, repair of the defect by recipient endothelium is so slow that edema and cloudiness of the overlying stroma develop and persist for long periods of time. Endothelial regeneration in the rabbit is associated with substantial recovery of corneal clarity.
190 citations