Noninvasive temporal detection of early retinal vascular changes during diabetes

Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression

Noninvasive temporal detection of early retinal vascular changes during diabetes

Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression

Hypoxic–ischemic injury causes functional and structural neurovascular degeneration in the juvenile mouse retina

Abstract Ischemic stroke is a major cause of long-term disabilities, including vision loss. Neuronal and blood vessel maturation can affect the susceptibility of and outcome after ischemic stroke. Although we recently reported that exposure of neonatal mice to hypoxia–ischemia (HI) severely compromises the integrity of the retinal neurovasculature, it is not known whether juvenile mice are similarly impacted. Here we examined the effect of HI injury in juvenile mice on retinal structure and function, in particular the susceptibility of retinal neurons and blood vessels to HI damage. Our studies demonstrated that the retina suffered from functional and structural injuries, including reduced b-wave, thinning of the inner retinal layers, macroglial remodeling, and deterioration of the vasculature. The degeneration of the retinal vasculature associated with HI resulted in a significant decrease in the numbers of pericytes and endothelial cells as well as an increase in capillary loss. Taken together, these findings suggest a need for juveniles suffering from ischemic stroke to be monitored for changes in retinal functional and structural integrity. Thus, there is an emergent need for developing therapeutic approaches to prevent and reverse retinal neurovascular dysfunction with exposure to ischemic stroke

Bcl-2 expression in pericytes and astrocytes impacts vascular development and homeostasis.

B-cell lymphoma 2 (Bcl-2) protein is the founding member of a group of proteins known to modulate apoptosis. Its discovery set the stage for identification of family members with either pro- or anti-apoptotic properties. Expression of Bcl-2 plays an important role during angiogenesis by influencing not only vascular cell survival, but also migration and adhesion. Although apoptosis and migration are postulated to have roles during vascular remodeling and regression, the contribution of Bcl-2 continues to emerge. We previously noted that the impaired retinal vascularization and an inability to undergo pathologic neovascularization observed in mice globally lacking Bcl-2 did not occur when mice lacked the expression of Bcl-2 only in endothelial cells. To further examine the effect of Bcl-2 expression during vascularization of the retina, we assessed its contribution in pericytes or astrocytes by generating mice with a conditional Bcl-2 allele (Bcl-