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NGF, BDNF, and NO in Myopic Subjects: Relationships Between Aqueous Levels and Lens Epithelial Cells' Activation
Maria De Piano1, Andrea Cacciamani2, Fabio Scarinci2
1Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS-Fondazione Bietti, 00184 Rome, Italy.
Abstract:
Several soluble mediators are activated during myogenesis and progression, and severe neurodegeneration, with related biomarkers, characterizes high myopia-related retinal atrophy. Targets of oxidative stress, epigenetics and neurogenic inflammation have been reported in the prospecting of some bioindicators to mirror retinal insults occurring in high myopia. The aim of the present study was to assess the expression of a few selected biomarkers belonging to the neurotrophin (NGF and BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3 and HD1) pathways. Sixty-five (65; 76.25 ± 9.40 years) specimens-aqueous, anterior capsule (AC), and lens epithelial cells (LEC)-were collected at the time of cataract surgery and used for ELISA (aqueous) and transcripts analysis (AC/LEC). Biosamples were grouped as emmetrope (23; 81.00 ± 6.70 years); myopia (24; 75.96 ± 7.30); and high (pathological) myopia (18; 70.56 ± 11.68 years), depending on axial length (AL) and refractive error (RE). Comparisons and correlations were carried out between myopic and high-myopic subgroups. NGF and BDNF were lowered in myopic samples; NGF and BDNF transcripts were differentially expressed in LEC, and their expression correlated positively with NGF and negatively with BDNF, with the expression of the αSMA phenotype. NGF and BDNF correlated negatively with NO and nitrites. Oxidative stress (iNOS/NOX1/NOX4 and KEAP1/NRF2) and epigenetic (DNMTα3/HD1) transcripts were upregulated in myopic LEC, compared with emmetropic ones. Herein, we prospect the contribution of NGF and BDNF in both neuroinflammation and neuroprotection occurring in this chronic disease.
Insights
This study investigated biomarkers in high myopia, finding reduced neurotrophic factors (NGF, BDNF) and increased oxidative stress and epigenetic markers in myopic eyes. These findings suggest a role for neuroinflammation and neuroprotection in myopia progression.
Area of Science:
- Ophthalmology and Vision Science
- Neuroscience
- Molecular Biology
Background:
- High myopia is linked to retinal atrophy and neurodegeneration.
- Oxidative stress, epigenetics, and neuroinflammation are implicated in high myopia.
- Biomarkers are sought to understand retinal insults in pathological myopia.
Purpose of the Study:
- To assess neurotrophin (NGF, BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3, HD1) biomarkers in myopia.
- To compare biomarker expression in emmetropes, myopes, and high myopes.
- To explore the role of NGF and BDNF in neuroinflammation and neuroprotection in myopia.
Main Methods:
- Collected aqueous humor, anterior capsule (AC), and lens epithelial cells (LEC) from 65 patients undergoing cataract surgery.
- Grouped samples into emmetropic, myopic, and high myopic categories based on axial length and refractive error.
- Utilized ELISA for aqueous samples and transcript analysis for AC/LEC, comparing myopic and high-myopic subgroups.
Main Results:
- NGF and BDNF levels were lower in myopic samples.
- NGF and BDNF transcripts showed differential expression in LEC, correlating with αSMA phenotype.
- NGF and BDNF correlated negatively with nitric oxide (NO) and nitrites.
- Oxidative stress (iNOS, NOX1/4, KEAP1/NRF2) and epigenetic (DNMTα3, HD1) transcripts were upregulated in myopic LEC compared to emmetropes.
Conclusions:
- NGF and BDNF may play a role in both neuroinflammation and neuroprotection in high myopia.
- Upregulation of oxidative and epigenetic markers suggests their involvement in myopia pathogenesis.
- Further research into these biomarkers could offer insights into managing myopia-related retinal damage.
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