INJURY-INDUCED UP-REGULATION OF BFGF AND CNTF MESSENGER-RNAS IN THE RAT RETINA

Focal mechanical injury to the retina has been shown to slow or preven t photoreceptor degeneration near the lesion site in two animal models of retinal degeneration, inherited retinal dystrophy in the Royal Col lege of Surgeons (RCS) and light damage in albino rats. Thus, when inj ured, 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 (C NTFR alpha); brain-derived neurotrophic factor (BDNF) and its receptor trkB; and insulin-like growth factor-1 (IGF-1) and IGFR-1 receptor (I GF-1R). After a single mechanical lesion to the subretinal space and r etina, there was a substantial increase in bFGF and CNTF expression th at persisted for the entire 10 d period of study. The increase in bFGF mRNA after injury was prompt and great in amplitude, while the elevat ion of CNTF mRNA was relatively slower. In addition, there was a trans ient increase in FGFR1 mRNA, In situ hybridizations showed that the el evation of bFGF and CNTF was localized to the vicinity of the lesion, The expression of GFAP (glial fibrillary acidic protein) mRNA also inc reased in response to injury. These findings strongly suggest that inc reases in endogenous bFGF and/or CNTF play key roles in injury-induced photoreceptor rescue.