Glaucoma along with Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS) is classified as a neurodegenerative disorder. There are resemblances in cellular events that lead to the development of glaucoma in the aforementioned diseases. Moreover, optic nerves from AD patients are characterized by the loss of RGCs, the earliest dying cells in glaucoma (Nowak et al. 2015). POAG accounts for three-quarters (74%) of all glaucoma cases and has a complex hereditary component; it has been associated with at least 20 loci in the human genome (Brad Bowling 2016).
BDNF is one of the key neurotrophic factors in glaucoma that is reduced in the optic nerve head and serum of POAG patients, suggesting that BDNF may be a biomarker for glaucoma. It is encoded by BDNF gene on chromosome11p14.1 (Kimura et al. 2016). BDNF mediates protection from apoptosis by p53 activation and exerts its pro-survival effects by binding to its receptor TrkB (Tropomyosin receptor kinase B), activating signaling pathways (Gupta et al. 2014). In animal models of glaucoma, BDNF delivery to the retina is reduced. However, injection of BDNF into the vitreous cavity of rats with experimentally elevated IOP leads to increased cell survival of RGCs (Nowak et al. 2015).
The rs2030324 polymorphism is located in the promoter site of BDNF gene; hence, it might have an influence on gene expression. Up to our knowledge, the rs2030324 SNP has not been investigated in patients of POAG in Egypt, neither on a wide nor on a narrow scale.
In the current study, Rt and Lt IOP and Rt and Lt C/D were significantly higher among glaucomatous patients than that among controls (P = 0.004 and P = 0.004 respectively). However, there was no statistical significant association between clinical parameters of both Rt and Lt (VA, IOP, C/D, and MD) and different BDNF genotypes SNP rs2030324 (P > 0.05). Moreover, there was no significance difference in BDNF genotypes or alleles frequencies between glaucoma patients and controls.
In contrast to our results, Nowak et al. (2015) found a significant higher frequency of the TT, TC genotype, and T allele of BDNF SNP rs2030324 (P < 0.001) in patients with POAG compared with the controls. Their study was performed by PCR-RFLP method on a large cohort of 769 unrelated Caucasian polish subjects: 363 POAG patients and 406 healthy controls. Their results showed association between BDNF genotypes and disease progression, where they found an increase in C/D in associated with TT BDNF genotype (P = 0.004).
This discrepancy between results may be due to different ethnic groups, racial differences, sample size, poorly characterized controls, and use of different methods for genotyping.
By analysis of BDNF expression level in the same study, Nowak et al. (2015) found no significant differences in serum BDNF mRNA expression levels between POAG patients and the controls (P > 0.05), while analysis of the BDNF expression level in relation to the clinical parameters showed a decrease of mRNA expression levels with a decrease of the RA value (rim area) (P = 0.011). RA reflects the real amount of nerve fibers in optic disc, which may indicate the protective role of BDNF in the development of glaucoma.
Another polymorphic site (196G/A) of BDNF gene was evaluated by Nowak et al. (2014) on 362 unrelated Caucasian polish subjects (169 POAG patients and 193 healthy controls). They found no significant association in frequency of BDNF (196G/A) genotypes or alleles and POAG. It seems that other polymorphic variants of BDNF gene may be involved in the development of POAG.