INVESTIGADORES
DORFMAN Damian
artículos
Título:
Ischemic conditioning protects the rat retina in an experimental model of early type 2 diabetes
Autor/es:
SALIDO EM; DORFMAN D; BORDONE M; CHIANELLI MS; SARMIENTO MI; ARANDA ML; ROSENSTEIN RE
Revista:
EXPERIMENTAL NEUROLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 240 p. 1 - 8
ISSN:
0014-4886
Resumen:
Ischemic conditioning protects the rat retina in an experimental model of early type 2 diabetes.
Salido EM, Dorfman D, Bordone M, Chianelli MS, Sarmiento MI, Aranda M, Rosenstein RE.
Source
Laboratory
of Retinal Neurochemistry and Experimental Ophthalmology, Department of
Human Biochemistry, School of Medicine/CEFyBO, University of Buenos
Aires/CONICET, Buenos Aires, Argentina.
Abstract
Diabetic
retinopathy is a leading cause of acquired blindness in adults, mostly
affected by type 2 diabetes mellitus (T2DM). We have developed an
experimental model of early T2DM in adult rats which mimics some
features of human T2DM at its initial stages, and provokes significant
retinal alterations. We investigated the effect of ischemic conditioning
on retinal changes induced by the moderate metabolic derangement. For
this purpose, adult male Wistar rats received a control diet or 30%
sucrose in the drinking water, and 3 weeks after this treatment, animals
were injected with vehicle or streptozotocin (STZ, 25mg/kg). Retinal
ischemia was induced by increasing intraocular pressure to 120 mm Hg for
5 min; this maneuver started 3 weeks after vehicle or STZ injection and
was weekly repeated in one eye, while control eyes were submitted to a
sham procedure. Fasting and postprandial glycemia, and glucose, and
insulin tolerance tests were analyzed. At 12 weeks of treatment, animals
which received a sucrose-enriched diet and STZ showed significant
differences in metabolic tests, as compared with control groups. Brief
ischemia pulses in one eye and a sham procedure in the contralateral eye
did not affect glucose metabolism in control or diabetic rats. Ischemic
pulses reduced the decrease in the electroretinogram a-wave, b-wave,
and oscillatory potential amplitude, and the increase in retinal lipid
peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic
protein, and vascular endothelial growth factor levels observed in
diabetic animals. In addition, ischemic conditioning prevented the
decrease in retinal catalase activity induced by T2DM. These results
indicate that induction of ischemic tolerance could constitute a fertile
avenue for the development of new therapeutic strategies to treat
diabetic retinopathy associated with T2DM.