Abstract
Abstract: :
Purpose: In this study, we quantified the histological and functional damage to the photoreceptors that occurs after intense light and determined the degree of protection which results from an optic nerve (ON) transection performed 7 or 21 days previously. In addition, we measured the levels of various trophic factors in the retina at different periods after ON transection and correlated these results with the amount of protection. Methods: Wistar rats received an ON transection in one eye while the fellow eye served as a control. ON transection was performed 3-4mm from the globe without damaging the retinal blood supply. After 7 or 21 days (7 day and 21 day groups, respectively), the rats were exposed to bright light (approximately 2000 lux) for 48h and allowed to recover for 5 days. Rats were then killed and total retinal mRNA and protein were extracted. The levels of rhodopsin and neurofilament light mRNAs and proteins were assessed using semi-quantitative RT-PCR and Western blotting. The electroretinogram (ERG) was recorded 1 day before and 5 days after bright light and histological sections were taken for analysis. In addition, rats were killed at various time points up to 21 days after ON transection and the retinas analysed for FGF-2, CNTF, NGF, GDNF, BDNF, GFAP and neurofilament light. Results: Intense light caused a reduction in the a- and b-waves of the ERG compared to baseline. In the 7 day group, both the a- and b-waves displayed significantly greater amplitudes in the ON-transected eye compared to the fellow control eye. A similar but statistically greater preservation of the a- and b-waves was observed in the 21 day group. Intense light also caused a reduction in the thickness of the outer nuclear layer and a loss of rhodopsin mRNA and protein. These losses were less pronounced in the ON-transected eyes. The amount of protection was significantly greater in the 21 day group. ON transection caused an upregulation of FGF-2, CNTF, NGF and GFAP but not of BDNF and GDNF. The change in FGF-2 correlated positively with the observed protection provided by the 7 and 21 day groups. Conclusions: The present studies show that ON transection provides both structural and functional protection to photoreceptors from bright light damage. The mechanism of action likely involves activation of retinal glial components which stimulate the release of certain trophic factors. The role of FGF-2 appears critical.
Keywords: photoreceptors • neuroprotection • growth factors/growth factor receptors