Glaucoma News: Indian Study Uncovers That High Incidence Of Glaucoma Among Punjabis Are Due To IL1B Gene Variants!

Glaucoma News: Glaucoma, a formidable group of optic neuropathies with a multifaceted etiology, stands as the second leading cause of blindness worldwide. Its impact is profound, characterized by the gradual degeneration of retinal ganglion cells (RGCs). Within this complex disease landscape, primary open angle glaucoma (POAG) and angle closure glaucoma (PACG) emerge as predominant clinical forms. In a groundbreaking study covered in this Glaucoma News report that was conducted by the collaborative efforts of Guru Nanak Dev University and Chandigarh University in Punjab, India, alongside the contributions of Thermo Fisher Scientific in Bengaluru and the All India Institute of Medical Sciences in New Delhi, researchers have delved into the genetic underpinnings of glaucoma among Punjabis. Specifically, the study identifies variants within the Interleukin (IL)1B gene as crucial determinants of high glaucoma incidence in this population.


 
IL1B and Glaucoma Pathogenesis
At the heart of glaucoma pathogenesis lies the Interleukin (IL)1B gene, a key candidate gene that profoundly influences the survival of retinal ganglion cells (RGCs). These cells, responsible for transmitting visual information from the eye to the brain, undergo gradual degeneration in glaucoma. Focusing on two critical polymorphisms within the IL1B gene, namely −511T > C and +3953C > T, the research aims to unravel their role as genetic risk factors for both primary open angle glaucoma (POAG) and angle closure glaucoma (PACG). The study encompasses a North Indian Punjabi cohort comprising 867 samples, carefully categorized into 307 POAG cases, 133 PACG cases, and 427 controls.
 
Study Design and Power of the Study
The research adopts a robust hospital-based case-control approach, collecting samples over a span of four years, from 2014 to 2018. The cases and controls were drawn from regular visits to two local hospitals in Amritsar - Sardar Bahadur Sohan Singh Eye Hospital and Baba Deep Singh Charitable Hospital. The controls were meticulously matched for age, sex, and ethnicity, with self-reported caste serving as a proxy for ethnicity. Rigorous genetic association analyses, diplotype assessments, and linkage disequilibrium analyses were performed, accompanied by corrections for confounding variables and multiple testing. To consolidate the findings, an updated meta-analysis was conducted, ensuring a holistic understanding of IL1B gene variants in glaucoma susceptibility.
 
Literature Survey Strategy
A comprehensive literature review spanning nearly two decades, from 2003 to 2021, formed a critical component of this study. The goal was to gather relevant data on IL1B gene polymorphisms, specifically rs16944 and rs1143634, and their association with primary open angle glaucoma (POAG). Multiple reputable sources, including PubMed, Medline, Google Scholar, and Embase, were meticulously explored to compile a comprehensive dataset that would enrich the study's contextual background.
 
Demographic and Clinical Characteristics
Delving into the demographic and clinical characteristics of the studied groups, the research presents a detailed snapshot o f the participants. The mean age among primary glaucoma cases was reported as 59.92 years, with a standard deviation of ±12.80. In the control group, the mean age was 59.46 years, with a standard deviation of ±11.57. Meticulous attention was given to sex distribution, revealing an equal representation of males and females in both cases and controls. This demographic homogeneity facilitated a nuanced exploration of genetic associations.
 
Study Characteristics of IL1B −511T > C (rs16944)
The meta-analysis component of the study incorporated a total of 39 articles, with a focus on 6 case-control studies. The cumulative dataset included 1571 cases and 1681 controls, spanning the years from 2003 to 2021. Notably, the meta-analysis encompassed diverse populations, with a specific emphasis on Chinese ancestry. This diversity in the study population underscored the global relevance and significance of IL1B gene variants in the context of glaucoma.
 
Discussion
The pivotal role of IL1B in glaucoma pathology is underscored by evidence from both ex-vivo and in-vivo studies. IL-1, a potent modulator of immunological and inflammatory responses, has been implicated in various chronic neurodegenerative diseases, including Parkinson's and Alzheimer's. In glaucoma, elevated intraocular pressure and ischemia trigger abnormal activation of glial cells, leading to persistent neuroinflammation and further harm to RGCs. The cytokine IL1B emerges as a critical player in this process, with significant increases observed in its levels in the aqueous humor of glaucoma patients compared to healthy controls.
 
IL1B's impact extends beyond inflammation, influencing glutamate homeostasis and potentially contributing to RGC death through various mechanisms. Excess glutamate, acting as a neurotoxin for RGCs, may trigger N-methyl-D-aspartate (NMDA) receptor-mediated influx of extracellular Ca2+ ions, initiating downstream signaling events culminating in cell death. IL1B may also contribute to RGC death through interactions with matrix metallopeptidases (MMP)-9, and intriguingly, it may upregulate the production of β-amyloid (Aβ) protein, a neurotoxic entity implicated in Alzheimer's disease. The study emphasizes the need for further exploration of these intricate pathways to unravel the complete picture of IL1B's involvement in glaucoma pathogenesis.
 
Conclusion
The culmination of this comprehensive study presents compelling evidence linking −511T > C and +3953C > T single nucleotide polymorphisms (SNPs) in the IL1B gene to genetic susceptibility in both POAG and PACG among the targeted North Indian Punjabi population. Notably, the research reveals a positive association of these IL1B variants with PACG in females, unveiling a sex-dependent aspect of genetic polymorphisms in glaucoma that has been relatively underexplored. These pioneering findings underscore the significance of IL1B gene variants in the intricate web of glaucoma pathogenesis among Punjabis.
 
As the study sets the stage for a deeper understanding of the genetic landscape of glaucoma, it calls for further replication studies in diverse populations and urges in-depth functional investigations. Solidifying the relevance of IL1B variants in the pathogenesis of primary glaucoma demands a concerted effort to expand the research horizon, ultimately paving the way for targeted interventions and personalized treatments in the battle against this pervasive vision-threatening condition.
 
The study findings were published in the peer reviewed journal: Experimental Eye Research.
https://www.sciencedirect.com/science/article/abs/pii/S001448352300341X
 
Thailand Medical News would like to add that while we have developed a comprehensive adjuvant treatment protocol fro Glaucoma that primarily involves a variety of phytochemicals to treat Glaucoma including normalizing IOP and also aiding in the regeneration of RGCs, we do not offer these protocols to any Punjabis at the moment due to bad experiences we have had with some of them including a Thai Punjabi Sikh who runs a website and app development company who ripped us off us by the development of this  substandard website that is laden with tech issues that prevents it from being ranked well, that costs us almost 1.6 million baht and also overcharging us for substandard hosting services for the last five years at a rate of about Thai baht 85,000 per year for the first 4 years. We also recently had a bad encounter with another Thai Punjabi who claimed he was from the US but who was lying to us about his background and was so pathetic that he did not even offer to buy us even a coffee when he wanted us to deliver to him the treatment herbs for free (costing more than Thai baht 420,000!) at a Starbucks outlet at a retail mall in Sukhumvit area! We advise all readers to be cautious when dealing with individuals from the Punjabi background.
 
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