Patterns of cell death, apoptosis and necrosis and the question of recovery in light induced retinal degeneration in the rat
Szczesny, P. J. (1996). Patterns of cell death, apoptosis and necrosis and the question of recovery in light induced retinal degeneration in the rat. (Unpublished Doctoral thesis, City, University of London)
Abstract
The purpose of this study was to investigate the early structural changes and the pattern of recovery in the rat retina after light damage. Methods: Albino rats were dark adapted for 36 hours. The control animals were sacrificed at the end of the dark adaptation period. The experimental animals were exposed for 2 hours to 1000 lux of white light, divided into 5 groups and killed at the following intervals: at the end of light exposure (0), 24, 48, 72 and 144 hours later. The right eyes were fixed in glutaraldehyde and processed for light and electron microscopy. The left eyes were processed for agarose gel electrophoresis of extracted retinal DNA to examine the pattern of DNA fragmentation occurring in various types of cell death. Results: Irreversible photoreceptor damage, observed after two hours of light exposure was observed in the lower temporal retina. It was characterized by condensation of cytoplasm, densification of outer segments and inner segments, including synapses, and pyknosis of the photoreceptor nuclei. Mitochondria, cilia and intracellular organelles and the arrangement of rod outer segment disks were, however, well preserved. Extensive auto and heterophagy (Muller cells) was observed but there was no inflammation. These changes were consistent with programmed cell death (apoptosis), which was confirmed by agarose gel electrophoresis showing a ladder formation characteristic for apoptosis up to 48 hours after light damage. Within 24 hours numerous photoreceptors showed, however, swelling and lysis of the inner segments, changes consistent with necrosis. Within a week chorioretinal adhesion was formed. Cell death in the retinal pigment epithelium was observed 24 hours after light exposure. The loss of the retinal pigment epithelium was followed by a breakdown of the blood retinal barrier resulting in serous retinal detachments and microcystic retinal oedema at its maximum 48 hours after exposure. Proliferation of cells in the inner nuclear layer was noted and an influx of macrophages, but no other inflammatory cells, was most pronounced between 48 and 72 hours after light damage. Lower nasal retina which primarily showed vesicular alterations of the rod outer segments as an acute response recovered normal morphology within one week. Conclusion: Diffuse white light can trigger regional retinal degeneration in a rat. Apoptosis of photoreceptors is an immediate retinal response to toxic light levels in albino rat retinae undergoing degeneration. Necrosis which was also recorded may be secondary in nature. In contrast, morphological recovery is observed in the regions in which vesicular alterations of disk membranes of photoreceptor outer segments were predominant. Such changes may signify disfunction of outer segment membranes and are enhanced by glutaraldehyde fixation.
Publication Type: | Thesis (Doctoral) |
---|---|
Subjects: | R Medicine > RE Ophthalmology |
Departments: | School of Health & Psychological Sciences > Optometry & Visual Sciences School of Health & Psychological Sciences > School of Health & Psychological Sciences Doctoral Theses Doctoral Theses |
Download (17MB) | Preview
Export
Downloads
Downloads per month over past year