title: Systemic IGF-I treatment inhibits cell death in diabetic rat retina.
abstract: 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.
authors.affiliation: Department of Ophthalmology, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Seigel
authors.forename: Sean B
authors.initials: SB
authors.lastname: Lupien
authors.forename: Lorrie M
authors.initials: LM
authors.lastname: Campbell
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Ishii
mesh_terms: 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
chemical_list: 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