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Diabetic Retinopathy and BDNF: A Review on Its Molecular Basis and Clinical Applications.

ABSTRACT: Impairment of neuroprotection and vasculopathy are the main reasons for the progression of diabetic retinopathy. In this review, we decided to illustrate the molecular and clinical aspects of diabetic retinal neuro-vasculopathy. We searched the Web of Science, PubMed, and Scopus databases with these keywords: "brain-derived neurotrophic factor" and "vascular endothelial growth factor" and/or "diabetic retinopathy." The most relevant in vitro and clinical trial studies were then extracted for final interpretation. Brain-derived neurotrophic factor and the vascular endothelial growth factor have pivotal roles in the pathogenesis of diabetic retinopathy. They have neuroprotective effects on the retina. However, there are controversial results on the relation between these two factors. Reviewing available articles, we have concluded that various concentrations of these molecules at different stages of retinopathy may exert different effects. Optimal doses of the brain-derived neurotrophic factor at the early stages of retinopathy may have a neuroprotective effect. In contrast, higher concentrations of brain-derived neurotrophic factor might induce inflammatory responses. Damage to the retinal cells due to metabolic alterations associated with diabetes and its consequence vasculopathy may also lead to changes in the ocular microenvironment and cytokines. Changes in cytokines result in the modification of neural cell receptors and the overproduction of vascular endothelial growth factor. It seems that controlling the optimal levels of neuroprotective molecules in the retinal tissue is the main step to halter diabetic retinopathy.

SUBMITTER: Afarid M

PROVIDER: S-EPMC7254082 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Diabetic Retinopathy and BDNF: A Review on Its Molecular Basis and Clinical Applications.

Afarid Mehrdad M Namvar Ehsan E Sanie-Jahromi Fatemeh F

Journal of ophthalmology 20200518

Impairment of neuroprotection and vasculopathy are the main reasons for the progression of diabetic retinopathy. In this review, we decided to illustrate the molecular and clinical aspects of diabetic retinal neuro-vasculopathy. We searched the Web of Science, PubMed, and Scopus databases with these keywords: "brain-derived neurotrophic factor" and "vascular endothelial growth factor" and/or "diabetic retinopathy." The most relevant in vitro and clinical trial studies were then extracted for fin ...[more]

PMID: 32509339

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Project description:Background: Diabetic retinopathy is a common microvascular complication in diabetic patients and is considered the main cause of visual loss worldwide. Periodontitis is a chronic inflammatory condition, which compromises dental supporting tissues. The chronic bacterial challenge in periodontitis is a persistent source of inflammatory mediators that may be associated with insulin resistance, increasing the risk of complications of diabetes mellitus. This systematic review aimed to summarize the evidence in the association between diabetic retinopathy and periodontitis. Methods: This review was registered under the number CRD 42019142267. A search strategy in five electronic databases and a gray literature source was performed based on the PECO acronym. After data extraction, the qualitative synthesis and risk of bias analyses were performed using the Newcastle-Ottawa scale. The level of evidence of all studies taken together was evaluated through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Out of the 253 citations screened, five cross-sectional studies met the eligibility criteria and were included in the qualitative analysis, in which two were judged to be of good quality, one as fair quality, and two as poor quality. Among the included studies, a significant relationship between the severity of periodontitis (CAL > 5 mm) and the severity of diabetic retinopathy (p < 0.05) was reported by four studies. Also, an association between both diseases in non-obese adults was found after adjustments [OR 2.206 (1.114-4.366); p = 0.0232). However, the analysis of evidence by GRADE assessment was rated as low. Conclusions: Although the results of individual studies suggest an association between diabetic retinopathy and periodontitis, the quality of the body of evidence was judged to be low by the GRADE approach. Further studies with larger sample sizes, adequate models of cofounders' adjustments, and prospective analysis of periodontitis and diabetes conditions ought to be conducted to clarify this association.

Project description:Patients with long-duration diabetes develop cardiovascular complications resulting in highly increased mortality and complications which affect the kidneys, eyes and peripheral nerves associated with high morbidity. Among the diabetic complications, damage in the eye, diabetic retinopathy, is the most common microvascular complication of diabetes. Diabetic retinopathy is a leading cause of vision-loss globally. It is characterized by a number of different patho-mechanisms including changes in vascular permeability, capillary degeneration, and finally at a late stage overshooting formation of new blood vessels. This expression analysis focused on the use of different experimental models for Diabetes Mellitus and its complications (for a review see 1: Al-Awar et al: Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; doi: 10.1155/2016/9051426). By that, we wanted to uncover the relative contributions of systemic hyperinsulinaemia and/or hyperglycemia to molecular regulations. The following models have been used: As insulinopenic, hyperglycemic model reflecting Type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p.) were used. Wistar rats without STZ injection served as non-diabetic controls. Male obese ZDF rats (Fa/Fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male lean ZDF rats (Fa/-) served as non-diabetic controls. Male obese ZF rats (Fa/Fa) hyperglycemia were used reflecting euglycemia and severe insulin resistance. Male lean ZF rats (Fa/-) served as controls. ZDF and ZF rats were obtained in two genotypes, obese (genotype fa/fa) and lean littermates (genotype Fa/?). All rats were housed in standard cages under a normal light-dark cycle for 16 weeks. All animals had free access to food and water. ZF and Wistar rats received a standard chow (Ssniff R/M) and ZDF rats received Purina 5008 chow. A group size of n=8 were used for all study groups. Wistar rats were rendered type-1 like hyperglycemic and hypoinsulinemic via a single injection of streptocotocin (STZ, 60mg/kg; i.p.) at 7 weeks of age. Obese ZDF rats (fa/fa) develop spontaneously a type-2 diabetes phenotype with persisting hyperglycemia and transient hyperinsulinemia (hyperglycemic, hypoinsulinemic). Obese ZF rats (fa/fa) develop insulin resistance with permanent hyperinsulinemia without concomitant hyperglycemia and no overt diabetes phenotype. Non STZ treated Wistar rats, lean ZDF littermates (Fa/?), and lean ZF littermates (Fa/?) served as controls. All groups were kept for 12 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays.

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Diabetic Retinopathy and BDNF: A Review on Its Molecular Basis and Clinical Applications.

Publications

Diabetic Retinopathy and BDNF: A Review on Its Molecular Basis and Clinical Applications.

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