These data suggest that there may be a link between the vasoregressive phenotype and increased expres-sion of the CNTF/LIF family of cytokines in the retina of TGR. CNTF expression parallels that of FGF2 in our TGR model. FGF2 knockout mice develop photoreceptor degeneration sug-gesting that FGF2 plays an important role in photoreceptor development and survival. Multiple degenerative and SB203580 injurious retina models yield upregulation of FGF2 suggesting the pleiotropic and essential role for FGF2 in survival of retinal cells. The lack of functional FGF2 could be a factor that causes the impaired protection of the diabetic retina from progressive vasoregression during the non-proliferative phase. Thus, in contrast to CNTF upregulation, FGF2 appears to be regulated as a response to injury type of tissue reaction in the TGR rat. The Mu ̀ˆller cell and astrocyte, which interconnect vessels and neurons through their end-foot processes, participate in neuro-protection and neuronal repair after injury. Thus, increased GFAP expression as early as after 1 month suggests that glial activation occurs in response to neuronal degeneration in TGR rats. However, upregulation of GFAP is unspecific, as it occurs in various retinal injury models such as axotomy, retinal ischemia, retinal detachment and diabetic retinopathy. In contrast to the diabetic model,SB431542 glial activation in the TGR model was not sufficient to induce VEGF, while bFGF upregulation is possibly the result of glial activation. Mutations in cilia genes or defective cilia genes are associated with renal abnormalities, retinal degeneration, liver and respira-tory diseases in patients. In a previous study using the TGR rat, defective polycystin-2 gene was found in the region of connection cilia of outer and inner segments of rod and cone photoreceptors. However, electron microscopy studies did not reveal any morphological cilia defects except photoreceptor degeneration in the TGR. The precise function of polycystin-2 in the retinal cilia remains unclear.