Effects of diabetic-like conditions and somatostatin/brimonidine on pericyte-ganglion cell co-culture models

DESIGN of STUDY. There is growing evidence for neurodegeneration as an early co-cause of diabetic retinopathy. Somatostatin and brimonidine may protect retinal cells, both microvascular and neuronal, from stress conditions. We have previously shown that they do not produce adverse effects on retinal pericytes. PURPOSE. We aimed at verifying the effects of hyperglycaemia and/or hypoxia, and those of somatostatin and brimonidine, on pericyte-ganglion cell co-culture models. METHODS. Human retinal pericytes (HRP) or rat ganglion cells (RGC-5) were exposed intermittently at 48 hrs intervals to high/physiological glucose for 8 days (intHG) and/or hypoxia for 48 hrs, with/without somatostatin or brimonidine. Conditioned media (CM) from the final two days were collected and used at 50% concentration to culture the other cell type. Control cells were cultured directly in physiological (NG), high glucose (HG) or intHG, with/without somatostatin/brimonidine. Cell proliferation and apoptosis were assessed. RESULTS. RGC-5 proliferation is decreased (-29.9%, p<0.005 vs NG) and apoptosis increased (+41.8%, p<0.05 vs NG) in intHG conditions. RGC-5 proliferate less when exposed to CM from HRP (-40.4% in NG-CM vs NG, p<0.05). When cultured in intHG-CM from HRP, RGC-5 show decreased proliferation (-13.1%, p<0.05) and increased apoptosis (+78.2%, p<0.005 vs NG-CM). CM from HRP in hypoxic conditions does not increase intHG-CM effects on RGC-5. As regards HRP, hypoxic conditions do not have direct or CM-mediated effects on them, but their proliferation is decreased (-20.9%, p<0.05 vs NG-CM) when they are exposed to intHG-CM from RGC-5. Somatostatin and brimonidine exert no effect, either positive or negative, in all cases. CONCLUSIONS. Intermittent high glucose conditions, both direct and mediated by HRP, decrease RGC-5 proliferation and increase their apoptosis, behaviour very similar to that shown by HRP. As we know that HRP are sensible to intermittent, but not stable, high glucose, we can hypothesize that HRP in stress conditions may release soluble factor(s) affecting RGC-5 viability. Somatostatin and brimonidine do not show any adverse effect on both pericytes and ganglion cells, neither direct nor mediated by the other cell type.