טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentBar-Yehuda Tehilla
SubjectA Potential Rat Model for Proliferative Diabetic
Retinopathy
DepartmentDepartment of Biotechnology
Supervisor Professor Emeritus Ido Perlman
Full Thesis textFull thesis text - English Version


Abstract

Proliferative Diabetic Retinopathy (PDR) is a blinding complication of diabetes characterized by retinal neovascularization, and is a complication unique to humans. Animal models of diabetes usually do not develop retinal neovascularization. Vascular Endothelial Growth Factor (VEGF) is a key player in the pathogenesis of PDR, yet VEGF alone is insufficient to cause retinal neovascularization.

This research thesis was aimed at creating an animal model for PDR, for testing the underlying pathological mechanisms and new therapeutic approaches, by an innovative approach - inducing over-expression of VEGF in diabetic rats' eyes.

16 Sprague-Dawley rats were used in this study and divided into four groups: (1a) healthy rats injected intraocularly with saline, (1b) healthy rats injected intraocularly with a recombinant Adenovirus that carries the VEGF gene (Ad-VEGF), (2a) Streptozotocin (STZ)-induced diabetic rats injected with saline and (2b) STZ-induced diabetic rats injected with Ad-VEGF. All rats were injected into their right eyes, while left eyes served as additional control.

Retinal blood vessels morphology was monitored in-vivo using a fundus camera. Micro-structural changes in retinal vessels were revealed following fluorescein-dextran angiography. Electroretinogram (ERG) recordings were used to assess retinal function. For some rats histological examination of the eye was done.

Control retinas (group 1a) exhibited normal function and structure throughout the experiment. The ocular pathologies observed in the other study groups were divided into 3 categories:

§                     Diabetes-related findings: Cataract formation, moderately decreased retinal function and high permeability of retinal blood vessels.

§                     Ad-VEGF-related findings: Twisting and curling of blood vessels, neovascularization of the iris and decreased retinal function.

§                     Diabetes and VEGF over-expression: Strongly reduced retinal function, hyphema, intra-retinal microvascular abnormalities (IRMAs), including neovascular tufts and capillary loops and fibrovascular tissues connecting the retina to the lens.

As expected, the pathological findings in the group of diabetic rats injected with Ad-VEGF (2b) were the most severe. IRMAs, especially neovascular tufts, are typical of the pre-proliferative stages of DR, heralding the onset of PDR. The finding of fibrovascular tissues also corresponds to the pathology of PDR in humans.

In summary, the results of this study support the hypothesis that VEGF over-expression in retinas of diabetic rats may become a practical animal model for proliferative diabetic retinopathy.