Endothelin: a new vasoactive ocular peptide.
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Biomedical subjects
Publications and source records attributed to U Chakravarthy.
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In a group of eighteen patients with uveal melanomas, seven underwent low-dose pre-enucleation irradiation of approximately 2000 cGy. All the tumours were propagated in tissue culture and the growth characteristics of tumour cells from irradiated eyes were compared with tumour cells from non-irradiated eyes. Cultures were observed with phase-contrast microscopy, and radioactive thymidine labelling was used to study cell turnover. Although tissue samples from peripheral areas of irradiated tumours produced a mixture of viable and non-viable cells, with reduced ability to attach to substrate, central regions of irradiated tumours contained viable cells which propagated freely in tissue culture.
Focal gamma irradiation was used to limit the intraocular extension of scar tissue which typically occurs after posterior perforating injury to the eye. Standard posterior perforating injuries were created in the right eye of forty-eight rabbits, half of which had the site of perforation focally irradiated using a Cobalt 60 ophthalmic plaque. Non-irradiated wounds healed with profuse formation of highly cellular and vascularised granulation tissue which invaded the vitreous to form contractile vitreo-retinal membranes. In irradiated eyes vitreo-retinal membrane formation was infrequent; the wounds showing only sparse granulation tissue with little or no extension into the vitreous cavity. Autoradiographic studies carried out in a second group of 40 animals showed that the episclera was the main source of the proliferating fibroblasts, and cell counts confirmed that the inflammatory and repair responses in irradiated wounds were both delayed and attenuated.
Plaques constructed with 125I were used to irradiate the sites of perforating ocular injuries in rabbits. An approximate dose of 16Gy given over a period of 6 days was shown to significantly reduce intraocular cellular proliferation when irradiation was commenced within 24 hours after injury. If irradiation was delayed until day 5, this reduction in cellular proliferation and intraocular membrane formation did not occur. Smaller radiation doses of approximately 6Gy given within 24 hours post-injury and administered over 6 days also reduced the extent of cellular proliferation but was not as effective as the 16Gy dose.
Standard perforating injuries were created in the right eye of 30 rabbits. Twenty of these had the site of injury irradiated using the radioactive ophthalmic 60Cobalt applicator. Vitreo-retinal membranes obtained from non-irradiated and irradiated eyes were propagated in vitro. The morphology and viability of the cells that grew as a monolayer was studied using phase, light and electron microscopy. The proportions of the different cell types that constituted the monolayer was determined using immunofluorescent staining techniques. Non-irradiated membranes elaborated an abundant outgrowth of healthy cells that were predominantly fibroblasts. Irradiated membranes developed a sparse outgrowth of cells with vacuolated cytoplasm and pyknotic nuclei indicating cell destruction. The majority of the surviving cells were glial, with fibroblasts and retinal pigment epithelial cells forming the remainder.
In 1965 the patient, aged 6, sustained a perforating eye injury which was repaired and a traumatic cataract was aspirated within five weeks. Five years later a Ridley Mk 2 A/C intraocular lens was inserted. Several episodes of blunt trauma occurred over a three year period following this procedure. This paper reports the clinical, corneal pachometric and specular microscopic findings of both traumatized and normal fellow eyes 18 years after the initial incident. The corneal endothelial mosaic of the traumatized right eye was very irregular in the vicinity of the initial site of perforation. These marked variations in cell size and shape were less apparent at peripheral corneal areas. The estimated cell loss to the traumatized eye was in the region of 74% although in spite of this corneal function was maintained. The effects of trauma on the corneal endothelium are discussed and a brief review of the literature presented.
A pilot study on the effect of localised irradiation applied to the site of a standard perforating injury in the rabbit eye, showed that gamma rays limited the formation of post-traumatic vitreoretinal membranes. A controlled study was therefore undertaken to confirm this observation. Twenty-four pairs of rabbits underwent a standard perforating injury in the right eye. One rabbit of each pair received a radioactive ophthalmic Cobalt applicator and the other a dummy applicator. Nineteen of 24 non-irradiated eyes developed vitreoretinal membranes, with associated traction retinal detachment. Only four of 24 irradiated eyes developed traction retinal detachment.
A controlled study was undertaken to assess the effect of gamma irradiation on post-traumatic intraocular cellular proliferation. A standard perforating injury in the posterior segment of the rabbit eye was used to induce intraocular cellular proliferation and vitreo-retinal membrane formation. The site of injury was irradiated with an ophthalmic Cobalt60 applicator which provided a continuous source of gamma rays. Non-irradiated eyes developed traction retinal detachments associated with post-traumatic vitreo-retinal membranes. Irradiated eyes developed attenuated membranes or atrophic retinal scars, with the retina remaining attached. The membranes in non-irradiated eyes were highly cellular with abundant collagen, while irradiated membranes had fewer cells within a sparse collagen matrix. The episcleral fibroblasts, on autoradiographic studies appeared to be the main source of the cells that formed the proliferating tissue in both non-irradiated and irradiated eyes. In irradiated eyes both the inflammatory response and division of fibroblasts were delayed and reduced.
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