Neuronal and neuroglial responses following retinal lesions in the neonatal rats

Abstract

Lesions were produced in the nasal-superior quadrant of rat retinas at 1 day postnatal. Both the optic fiber and ganglion cell layers were destroyed at the lesion site. Retrograde changes in the more peripherally located ganglion cell bodies, their optic fibers, and neuroglia were monitored by light and electron microscopy. No optic fibers remained in the region peripheral to the lesion site after 2 days postoperative (DPO). Neither regenerative sprouting nor axonal ingrowth from late-maturing ganglion cells in the retinal periphery was observed. Cell death of the large and the majority of medium ganglion cell bodies was very rapid as was clearing of the degeneration products. These processes peaked at 1 DPO and were complete by 2 DPO. Microglia and Mueller cell cytoplasm actively phagocytized degenerating ganglion cell bodies and their optic fibers. A stable population of cell bodies in the ganglion cell layer peripheral to the lesion remained intact from 2 DOP to 21 DPO. The surviving somata were consistently 65% of the control ganglion cell population, and they remained after their axons had degenerated. The cell bodies measured 6-12.1 micron in diameter, a range which included the small cell population and a few of the medium cells. Dendritic patterning, used to designate ganglion cell types, corroborated their classification as small and medium ganglion cells. Morphological changes in these perikarya due to axotomy were limited to a mild chromatolytic response.

Temporal regulation of CD81 following retinal injury in the rat

“…The levels of GFAP immunoreactivity increased with time. From the third day after injury, both astrocytes and Müller cells showed up-regulation of GFAP similar to that previously described [12,15,16]. The levels of GFAP continued to increase so that, by 7 days after injury, two distinct cellular responses were observed at the site of injury.…”

“…As in the brain and spinal cord, a dramatic up-regulation of glial fibrillary acidic protein (GFAP) follows retinal injury. This up-regulation of GFAP marks reactive retinal astrocytes [12,16], which hypertrophy and increase their expression of the intermediate filament protein GFAP [3,13,18]. Müller glia and the retinal pigment epithelium (RPE), which are unique to the retina, also demonstrate characteristic responses to injury.…”

“…The response of the retina to trauma involves well-characterized cellular reactions [16], many of them similar to responses that occur in other parts of the central nervous system. As in the brain and spinal cord, a dramatic up-regulation of glial fibrillary acidic protein (GFAP) follows retinal injury.…”

Protection of Retinal Ganglion Cells from Natural and Axotomy-Induced Cell Death in Neonatal Transgenic Mice Overexpressing bcl-2

“…We showed previously that a section to the optic nerve in the neonatal rat induces the appearance of chromatin condensation (pyknosis) in ganglion cells (Miller and Oberdorfer, 1981;Beazley et al, 1987;Rabacchi et al, 1994a) as well as nuclear DNA fragmentation, as assessed by applying a method of in situ detection of DNA fragmentation (TUNEL) (Gavrieli et al, 1992;Rabacchi et al, 1994a). We therefore examined the appearance of pyknotic cells and DNA fragmentation in wild-type and bcl-2 transgenic animals after transection of the optic nerve.…”

Genetic Networks Modulating Retinal Injury

“…Others have described the neuronal and glial response after retinal breaks induced with scrapes [Miller and Oberdorfer, 1981;Maclaren, 1996] and laser photocoagulation lesions [Humphrey et al, 1993]. Steven K Fisher's group examined the cellular response to the separation of the neural retina from the RPE layer in a model of retinal detachment in cats [Anderson et al, 1983].…”