Abstract
ObjectiveCiliary neurotrophic factor (CNTF) has been evaluated as a candidate therapeutic agent for diabetes and its neural complications. However, its role in diabetic retinopathy has not been fully elucidated.MethodsThis is a randomized unblinded animal experiment. Wistar rats with streptozocin (STZ)-induced diabetes were regularly injected with CNTF or vehicle control in their vitreous bodies beginning at 2 weeks after STZ injection. A total of five injections were used. In diabetic rats, the levels of CNTF and neurotrophin-3 (NT-3) were evaluated by enzyme-linked immunosorbent assays (ELISA) and real-time PCR. The abundance of tyrosine hydroxylase (TH) and β-III tubulin was detected by western blot. Transferase-mediated dUTP nick-end labeling staining (TUNEL) was used to detect cell apoptosis in the retinal tissue. The activation of caspase-3 was also measured.ResultsThe protein and mRNA levels of CNTF in diabetic rat retinas were reduced compared to control rats. In addition, retinal ganglion cells (RGCs) and dopaminergic amacrine cells appeared to undergo degeneration in diabetic rat retinas, as revealed by transferase-mediated dUTP nick-end labeling staining (TUNEL). Tyrosine hydroxylase (TH) and β-III tubulin protein levels also decreased significantly. Intraocular administration of CNTF rescued RGCs and dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of β-III tubulin and TH expression, thus demonstrating its therapeutic potential.ConclusionOur study suggests that early diabetic retinal neuropathy involves the reduced expression of CNTF and can be ameliorated by an exogenous supply of this neurotrophin.
Highlights
Diabetic retinopathy (DR) is the leading cause of visual impairment and preventable blindness throughout the world [1, 2], representing a significant socioeconomic cost to healthcare systems [3,4,5]
The mean value obtained for non-diabetic rats was set as 100% for each protein species, and tyrosine hydroxylase (TH) protein levels were standardized to GAPDH levels
We found that TH protein levels were significantly lower in diabetic than in non-diabetic rats (p < 0.01, n = 4 rats in group) (Fig. 1)
Summary
Diabetic retinopathy (DR) is the leading cause of visual impairment and preventable blindness throughout the world [1, 2], representing a significant socioeconomic cost to healthcare systems [3,4,5]. Laser photocoagulation is applicable only at advanced stages of disease and is associated with significant adverse effects, such as moderate vision loss, reduced color vision, reduced contrast sensitivity [7], infection, and glaucoma [8]. Vitreoretinal surgery is another option, but it is an expensive treatment that can only be performed by experienced vireoretinal surgeons and is typically reserved for cases where blindness occurs due to proliferative DR (PDR) [9]. No drugs are currently available that effectively prevent the incidence or progression of DR in these critical early stages.
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