ABSTRACT
Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.
ABSTRACT
AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.
ABSTRACT
Circular RNA (circRNA) is a closed loop molecule generated by the back-splicing of pre-mRNA.CircRNA can act as microRNA (miRNA) sponge or combine with proteins and RNAs to form complexes, having functions of regulating the host gene expression and protein translation, which is of great significance in physiology and pathophysiology.Aberrant expression of specific circRNA exists in multiple ophthalmic diseases.As miRNA sponge that regulates the expression of target genes, circRNA may induce the various dysfunctions of eye cells, resulting in neovascularization, vascular leakage, inflammation, neurodegeneration, lens opacity, tumor growth and other pathologic changes, which plays an important role in the development and progression of eye disorders.In this article, the current expression characteristics of circRNA and the gene regulatory networks mediated by circRNA in several ophthalmic diseases were reviewed to explore the value of circRNA being diagnostic biomarkers and new therapeutic targets in ophthalomology.
ABSTRACT
@#Diabetic retinopathy(DR)has always been considered as microangiopathy. However, a large number of studies have confirmed that DR can not only cause retinal angiopathy, but also cause retinal neurodegeneration. Recently, more and more evidence also shows that retinal neurodegeneration occurred before retinal angiopathy in the early stage of DR, and retinal neurodegeneration may be involved in the occurrence and development of microvascular abnormalities. At present, the mechanism of diabetic retinal neurodegeneration is not very clear. This paper reviews the research progress on the mechanism of diabetic retinal neurodegeneration in recent years.
ABSTRACT
Background: Neurodegeneration of retina (retinal diabetic neuropathy) is the earlier sign of diabetes mellitus before the appearance of any vascular sign of diabetic retinopathy. Hence, through neurodegenerative changes, we can diagnose and monitor the early neuronal damage of the retina. Objectives: The objective of the study were to establish whether the retinal neurodegeneration is earlier than vasculopathic changes in patients with diabetes and their relationship with the duration of diabetes. Materials and Methods: A total of 180 diabetic patients and 164 healthy controls were collected from a rural-based tertiary care hospital in West Bengal for this cross-sectional study. All have gone through proper history taking, comprehensive ocular examinations and spectral-domain optical coherence tomography imaging to detect the thickness of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL). Results: Our study showed that the RNFL thickness of the right and left eyes for the cases was 37.62 μm and 37.68 μm, respectively, and that for controls were 39.68 μm and 39.70 μm, respectively. The GCL thickness of the right and left eyes was 32.63 μm and 32.43 μm, respectively, in cases and that for controls were 33.73 μm and 33.87 μm, respectively. In respect of the duration of diabetes, mean RNFL thickness of the right and left eyes for <1 year, 1–2 years, and >2 years was 40.20 μm and 40.03 μm; 38.17 μm and 38.31 μm; and 35.48 μm and 35.69 μm, respectively. Mean GCL thickness of the right and left eyes for <1 year, 1–2 years, and >2 years was 34.25 μm and 33.72 μm; 31.98 μm and 31.44 μm; and 30.82 μm and 31.35 μm, respectively. The data were analyzed by appropriate statistical methods. Conclusion: This study showed that thinning of RNFL and GCL occurred in diabetes before the appearance of microaneurysm.