Systemic IGF-I treatment inhibits cell death in diabetic rat retina.
Diabetic retinopathy can result in apoptotic cell death of retinal neurons, as well as significant visual loss. It is further known that insulin-like growth factor (IGF) levels are reduced in diabetes and that IGF-I can prevent cell death in many cell types. In this study, we tested the hypothesis that systemic treatment with IGF-I could inhibit death of neuroretinal cells in diabetic rats by examining the expression of proapoptotic markers. In diabetic rat retina, the number of TUNEL-immunoreactive cells increased approximately sixfold in the photoreceptor layer (P<.001) and eightfold in the inner nuclear layer (INL; P<.001); phospho-Akt (p-Akt; Thr 308) immunoreactivity increased eightfold in the ganglion cell layer (GCL; P<.001) and threefold in the INL (P<.01). Subcutaneous IGF-I treatment significantly reduced the number of TUNEL (P<.001) and p-Akt immunoreactive retinal cells (P<.05) in diabetic rats approximately to the level of the nondiabetic group. Qualitative results showed that caspase-3 and BAD immunoreactivities were also elevated in diabetes and reduced in IGF-I-treated animals. Elevated TUNEL and p-Akt immunoreactivities were localized to distinct cell layers in the retina of diabetic rats. Early intervention with systemic IGF-I reduced the presence of proapoptotic markers indicative of neuroretinal cell death, despite ongoing hyperglycemia and weight loss. The eye is a special sensory organ, and these data show that cell loss in the nervous system, even in uncontrolled diabetes, can be prevented by IGF-I administration.
Seigel
Gail M
GM
Department of Ophthalmology, University at Buffalo, Buffalo, NY 14214, USA.
Lupien
Sean B
SB
Campbell
Lorrie M
LM
Ishii
Douglas N
DN
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D016923:Cell Death / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006943:Hyperglycemia / Q000188:drug therapy; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D051058:Oncogene Protein v-akt; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology*; D015431:Weight Loss / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000032:analysis
D051017:Apoptosis Regulatory Proteins; C494821:Bad protein, rat; D051025:bcl-Associated Death Protein; D007334:Insulin-Like Growth Factor I; D051058:Oncogene Protein v-akt; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases