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Purpose: To examine mRNA expression of neurotrophic factors in the retina after exposure to bright light., Methods: Male adult Sprague-Dawley rats were exposed to light of 115-130 ft-c. Retinas were collected after 1, 2, 4 or 7 days of exposure. Northern blot analysis was performed to determine mRNA levels for the following factors and their receptors: basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), acidic fibroblast growth factor (aFGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and glial fibrillary acidic protein (GFAP). Expression of bFGF, CNTF and GFAP was localized by in situ hybridization., Results: Exposure to light of 115-130 ft-c resulted in a substantial increase in bFGF and CNTF expression that persisted during the entire 7-day period of exposure. The peak expression of bFGF was almost 9-fold at day 2. The increase in CNTF mRNA reached a maximum of 6-fold at day 4. A small increase (50%) in IGF-1 mRNA was also seen at day 4. Among the receptors, an elevation of 3-fold in FGF receptor 1 (FGFR-1) was observed at day 2. There was also a small increase (70%) in IGF-1 receptor (IGF-1R) at day 2. In addition, the expression of GFAP showed a rapid elevation of about 8-fold by day 1 and 9-fold by day 2, and 18-fold by day 4. There was, however, no significant alteration in the expression of aFGF and BDNF. In situ hybridizations showed that the elevation of bFGF, CNTF and GFAP occurred across the entire retina with especially prominent increases over specific layers for each gene., Conclusions: Continuous exposure to bright light upregulates bFGF, CNTF, FGFR-1 and GFAP expression in the rat retina. The pattern of induced expression closely resembles that induced by mechanical injury, implying a common underlying mechanism.

Focal mechanical injury to the retina has been shown to slow or prevent photoreceptor degeneration near the lesion site in two animal models of retinal degeneration, inherited retinal dystrophy in the Royal College of Surgeons (RCS) and light damage in albino rats. Thus, when injured, the rat retina activates a self-protective mechanism to minimize damage. To identify injury responsive factors and cells, we examined the mRNAs for the following factors and some of their receptors: basic and acidic fibroblast growth factors (bFGF, aFGF) and FGF receptor-1 (FGFR1); ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha); brain-derived neurotrophic factor (BDNF) and its receptor trkB; and insulin-like growth factor-1 (IGF-1) and IGFR-1 receptor (IGF-1R). After a single mechanical lesion to the subretinal space and retina, there was a substantial increase in bFGF and CNTF expression that persisted for the entire 10 d period of study. The increase in bFGF mRNA after injury was prompt and great in amplitude, while the elevation of CNTF mRNA was relatively slower. In addition, there was a transient increase in FGFR1 mRNA. In situ hybridizations showed that the elevation of bFGF and CNTF was localized to the vicinity of the lesion. The expression of GFAP (glial fibrillary acidic protein) mRNA also increased in response to injury. These findings strongly suggest that increases in endogenous bFGF and/or CNTF play key roles in injury-induced photoreceptor rescue.

Recent demonstrations of survival-promoting activity by neurotrophic agents in diverse neuronal systems have raised the possibility of pharmacological therapy for inherited and degenerative disorders of the central nervous system. We have shown previously that, in the retina, basic fibroblast growth factor delays photoreceptor degeneration in Royal College of Surgeons rats with inherited retinal dystrophy and that the growth factor reduces or prevents the rapid photoreceptor degeneration produced by constant light in the rat. This light-damage model now provides an efficient way to assess quantitatively the survival-promoting activity in vivo of a number of growth factors and other molecules. We report here that photoreceptors can be significantly protected from the damaging effects of light by intravitreal injection of eight different growth factors, cytokines, and neurotrophins that typically act through several distinct receptor families. In addition to basic fibroblast growth factor, those factors providing a high degree of photoreceptor rescue include brain-derived neurotrophic factor, ciliary neurotrophic factor, interleukin 1 beta, and acidic fibroblast growth factor; those with less activity include neurotrophin 3, insulin-like growth factor II, and tumor necrosis factor alpha; those showing little or no protective effect are nerve growth factor, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor I, heparin, and laminin. Although we used at least one relatively high concentration of each agent (the highest available), it is still possible that other concentrations or factor combinations might be more protective. Injecting heparin along with acidic fibroblast growth factor or basic fibroblast growth factor further enhanced the degree of photoreceptor survival and also suppressed the increased incidence of macrophages produced by either factor, especially basic fibroblast growth factor. These results now provide the impetus for determining the normal function in the retina, mechanism(s) of rescue, and therapeutic potential in human eye diseases for each agent.