Research Article: Role of BDNF in form-deprivation myopia progression in guinea pigs
Abstract:
This study investigated the effects of intravitreal administration of brain-derived neurotrophic factor (BDNF) on the progression of form-deprivation myopia (FDM) in a guinea pig model and explored the associated molecular mechanisms.
In Experiment 1, 45 pigmented guinea pigs (aged 3 weeks) were randomly assigned to 5 groups to assess the impact of varying BDNF concentrations (50, 100, and 200 ?g/mL) delivered via intravitreal injection following 4 weeks of monocular form deprivation. Axial length and refractive error were measured at baseline, after the deprivation period, and one day post-injection. In Experiment 2, 36 guinea pigs were allocated into 4 groups to further assess ocular structural changes and underlying molecular pathways. Hematoxylin and eosin (H&E) staining, immunofluorescence, optical coherence tomography (OCT), and western blotting were used to analyze morphological changes in the retina, choroid, and sclera, as well as the expression of BDNF, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) in the retina.
The 200 ?g/mL BDNF concentration significantly inhibited axial elongation and myopic refractive shifts in eyes with FDM. Immunofluorescence localized BDNF expression predominantly to the retina and choroid. Both H&E staining and OCT imaging demonstrated increased retinal and choroidal thickness and improved scleral collagen organization following BDNF administration. Western blot analysis revealed a downregulation of PI3K, AKT, eNOS, and nNOS expression in the retina of FDM-affected eyes treated with BDNF.
Intravitreal injection of 200 ?g/mL BDNF effectively attenuated the progression of FDM in guinea pigs. This effect may be mediated through modulation of the PI3K/AKT/eNOS/nNOS signaling pathway. These findings support BDNF as a potential therapeutic target for myopia control.
Introduction:
Myopia, a common refractive error, has emerged as a major global public health concern due to its rapidly rising prevalence. Epidemiological projections estimate that by 2050, approximately 4.758 billion individuals, accounting for 49.8% of the global population will be affected by myopia, with 938 million individuals (9.8%) developing high myopia ( 1 ). High myopia is associated with an increased risk of serious ocular complications, including cataracts, glaucoma, chorioretinal degeneration, and retinal…
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