Histological Study on the Therapeutic Effect of Gene Modified Bone Marrow Hemopoeitic Stem Cells (BMHSCs) Versus Unmodified BMHSCs Derived Exosomes in Early Diabetic Retinopathy Male Rat Model

Background and Objectives: Globally, one of the main causes of blindness and vision impairment in the working class is diabetic retinopathy (DR). The goal of the current study was to evaluate and investigate the therapeutic benefits of bone marrow hemopoietic stem cells (BMHSCs) modified by RPE65 and CYP46a1 gene versus unmodified BMHSCs derived exosomes in streptozotocin (STZ) induced early diabetic retinopathy (DR) in male albino rat model. Materials and Methods: 32 adult male rats were divided into: Donor Group, Group І (Control Group), Group II (DR Group): given STZ (50 mg/kg), once by intraperitoneal (IP) injection. Group III (DR, BMHSCs-EXOs treated Group): 2 weeks following confirmation of diabetes BMHSCs-EXOs, were injected in 4 doses IP, Group IV (DR, Gene modified BMHSCs treated Group): 2 weeks following confirmation, RPE65 and CYP46a1 transfected BMHSCs injected once IP. Rats were sacrificed 6 weeks, following day of confirmation of diabetes. Electroretinogram (ERG), serological, biochemical, histological, immunohistochemical, morphometric, fluorescent microscopic and statistical studies were performed. Quantitation of RPE65 and CYP46a1 genes and proteins was done. Results: In group II, mean amplitudes of a and b waves in ERG denoted significant increase and decrease respectively, mean values of blood glucose indicated significant increase, mean Lipid peroxidation (LPO) and Glutathione peroxidase (GPx) values indicated significant increase and decrease respectively. Morphological changes indicative of inflammation progressing to degeneration were found. Group III revealed less inflammatory and degenerative changes. Group IV expressed obvious regression of previous changes. Morphological and immunohistochemical data were confirmed morphometrically. Mean RPE65 and CYP46a1 gene values, and RPE65 and CYP46A1 protein values indicated a significant decrease in group II versus all groups, in group III versus groups I and IV. Conclusion: RPE65 and CYP46a1 gene modified BMHSCs therapeutic effect was more pronounced than BMHSCs-EXOs therapeutic effect.