There is no compelling evidence until now that Müller cells are the primary sites affected during any retinal disease. However, there are many retinal conditions in which Müller cells appear to play a prominent role. Studies of diabetic retina and animal models of hyperglycemia have revealed changes in Müller cell morphology, protein expression, and physiology well in advance of detectable retinopathy.
1 12 23 24 25 26 There are numerous recent reports that improved our knowledge regarding the biochemical processes underlying diabetic retinopathy (for reviews, see Refs.
8 ,
27 ,
28 ). Particular attention has been focused on the role of growth factors in the pathogenesis of diabetic retinopathy. In fact, there is now evidence that the development of diabetic retinopathy is a multifactorial process implying growth factors.
29 Histologic studies have demonstrated the presence of growth factors (mainly VEGF, PDGF,
30 and bFGF
31 ) and their receptors and/or their mRNA in preretinal membranes of patients with proliferative diabetic retinopathy. The expression of growth and trophic factors by HMCL-I and -II was thus compared with that in normal Müller cells. Our results indicate the expression of VEGF and bFGF by HMCLs and NHMCs but no expression of PDGF. The RT-PCR results obtained with HMCLs show that a significantly larger expression is obtained with bFGF than in NHMCs. bFGF is a mitogen peptide that has a growth-promoting effect
32 33 and has been shown to stimulate proliferation of retinal Müller cells.
34 35 36 The higher rate of proliferation of HMCLs could thus be correlated with the presence of a stronger expression of bFGF in those cell lines. As observed for both HMCLs when compared with NHMCs, a recent study
37 showed an increase in the expression of bFGF in the glial cells of rat diabetic retina compared with nondiabetic rats. Furthermore, Patel et al.,
38 observed that the immunoreactivity for EGF and TGF-α was generally stronger in diabetic retinas than in normal retinas. However, in our experiments, EGF and TGF-α transcripts are both expressed less by HMCLs than by NHMCs. These results are difficult to compare given that Patel et al.
38 made their observations in retina sections, where immunoreactivity was difficult to attribute to individual cells. Moreover, IGF-I is known to increase glucose transport in glial cells,
39 and insulin mRNA expression has been found in cultured Müller cells.
40 We also found that IGF-I is expressed by NHMCs at approximately the same level as in the HMCLs. Previous studies showed that CNTF was present in Müller cells from normal retina,
41 42 43 which is consistent with our observations. Indeed, we found RNA expression of CNTF in both HMCLs and NHMCs. Different immunohistochemical analyses have demonstrated that exogenous BDNF can diffuse throughout the retina
44 and bind to Müller cells
45 which express both BDNF receptors.
46 47 48 In addition, Seki et al.,
49 have determined that Müller cells of mammals normally contain BDNF, which is consistent with our results. Indeed, we found RNA expression of BDNF by both HMCLs and NHMCs.