Mesenchymal stem cells (MSC) are considered to have important value in the treatment of various diseases because of their low immunogenicity, transferability, and strong tissue repair capacity. Stromal cell derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) pathway plays an important role in migration of MSC. The induction of homing of MSC to retina by regulating SDF-1/CXCR4 may exert the curative effect on diabetic retinopathy to greatest exent.
Diabetic retinopathy (DR) isacommon cause of blindness, its occurrence and development are the synergic results of multiple factors. Current studies suggest that inflammation and inflammatory factor has an important role in the pathogenesis of DR. The occurrence and development of DR are closely related with interleukins, intercellular adhesion molecules, hasten factors, tumor necrosis factor, C-reactive protein etc. Mesenchymal stem cells (MSCs) are pluripotent cells derived from the mesoderm and have multiple differentiation potentials, and anti-inflammatory and immunosuppressive function. Recent studies shown that MSCs transplantation can protect damaged retina by inflammatory regulation, which becomeanew research direction for DR treatment.
Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab (Avastin) in diabetic rats. Methods Forty male Sprague Dawley (SD) rats were randomly divided into normal group (Group A, 10 rats) and diabetes mellitus group (30 rats). The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model. And then randomly divided into diabetic retinopathy (DR) group (Group B,10 rats), the rats were not intervened; the left eyes of the other 20 rats were intravitreal injected with bevacizumab 3 mu;l (25 mg/ml) for 3 times as experimental group (Group C) ; the right eyes of the 20 rats were not intervened as experimental control group (Group D). 20 days after last intravitreal injection, retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide (EB) stained retinal flat mounts; retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining. Results F-ERG showed that, the differences of a-and b-waves, the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A, B, C and D were significant (F=33.165, 36.162,19.955, 23.243; P＝0.000); the differences of a-wave amplitude between group A,B,C and D was not significant (F=0.097,P＝0.961). Retinal blood vessel pattern was normal in Group A; retinal vascular vessels were tortuous and irregularly expanded in Group B; retinal vascular vessels of Group C were regular and thinner than Group A; microaneurysm were showed in Group D. Light microscope displayed that the layers of the rat retina of Group A were regular, the retinal architectures of Group B were irregular, the retinal layers were regular in Group C, the retinal layers were irregular in Group D. Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer（GCL）. Conclusion Repeated intravitreal injection of bevacizumab is toxic to retina of diabetes mellitus rats.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
Dysregulation and activation of immune processes are important in age-related macular degeneration (AMD) pathogenesis. The single nucleotide polymorphism of complement factor H is widely recognized as a risk factor to AMD. Over-activation of nod-like receptor3 and polymorphism of Toll-Like Receptor 3 also associated with AMD. Except for innate immune processes, adaptive immunity also play a critical role in AMD, a growing body of evidence supports that auto-antibodies and T cells are related with AMD. Additionally A2E and lipid oxidation byproducts might also have a role in AMD pathogenesis.