Mind over Microbes: Investigating the Interplay between Lifestyle Factors, Gut Microbiota, and Brain Health.

BACKGROUND: The gut microbiota (GM) of the human body comprises several species of microorganisms. This microorganism plays a significant role in the physiological and pathophysiological processes of various human diseases. METHODS: The literature review includes studies that describe causative factors that influence GM. The GM is sensitive to various factors like circadian rhythms, environmental agents, physical activity, nutrition, and hygiene that together impact the functioning and composition of the gut microbiome. This affects the health of the host, including the psycho-neural aspects, due to the interconnectivity between the brain and the gut. Hence, this paper examines the relationship of GM with neurodegenerative disorders in the context of these aforesaid factors. CONCLUSION: Future studies that identify the regulatory pathways associated with gut microbes can provide a causal link between brain degeneration and the gut at a molecular level. Together, this review could be helpful in designing preventive and treatment strategies aimed at GM, so that neurodegenerative diseases can be treated.

Effectiveness of integrated approach of yoga therapy versus usual care in management on chronic low back pain patients: A randomized controlled pilot study.

BACKGROUND: Chronic low back pain is associated with both psychological and functional limitation. Yoga therapy has been shown to improve both the aspects. The present study was planned to evaluate integrated approach of yoga therapy with usaul care. AIMS: This controlled randomized trial was done to evaluate the clinical and molecular changes resulting from integrated approach of yoga therapy (IAYT) as an adjunct regimen and compared it with usual care for the management of chronic low back pain patients. MATERIAL AND METHODS: We enrolled 29 adult patients with non-specific chronic low back pain (CLBP). Patients were randomly divided into two groups. The control group received the usual care of treatment as per institutional protocol. The yoga group received IAYT as an adjunct to usual care. Primary outcomes were pain intensity assessed by verbal numerical rating scale (VNRS) and functional ability assessed by Modified Oswestry Disability Index (MODI). Secondary outcomes were pain catastrophizing, quality of life, fear of movement related to CLBP, type of pain, levels of ß-endorphin and TNF-α, and salivary CGRP. All parameters were measured at baseline, 1 and 3 months. RESULTS: A Significant decrease in VNRS score at 1 and 3 months was observed in both the groups with the yoga group showing a more significant reduction in pain over time than the control group (p = 0.036). MODI improved significantly only in the yoga group at 1 and 3 months. Intergroup comparison revealed significantly better MODI over time in the yoga group (p < 0.001). DN4, PDQ, PCS, HADS (anxiety), and Euro QOL had a statistically significant improvement at 1 and 3 months in the yoga group compared with the control group. The HADS (depression) had a statistically significant reduction scores in the yoga group at 3 months compared with the control group (p = 0.012). There was a significant reduction in TNF-α values in the yoga group compared with baseline (p = 0.004). CONCLUSION: IAYT therapy helped in addressing the psychological components of pain and improved quality of life patients with chronic low back pain compared with usual care.

Gene networks determine predisposition to AMD.

PURPOSE: AMD genetic studies have revealed various genetic loci as causal to AMD pathology. We have described the genetic complexity of Indian AMD by describing the interaction of genotypes and subsequent changes in protein expression under the influence of environmental factors. This can be utilized to enhance the diagnostic and therapeutic efficacy in AMD patients. DESIGN: Genotype association was studied in 464 participants (AMD =277 & controls = 187) for eight genetic variants and their corresponding protein expression METHODS: SNP analysis and protein expression analysis was carried out in AMD and controls in tandem with longitudinal assessment of protein levels during the course of AMD pathology. ANCOVA and contrast analysis were used to examine the genotypic interactions and corresponding alterations in protein levels. In order to identify the important genetic variants Logistic Regression (LR) modeling was carried out and to authenticate the model Area under the Receiver Operating Characteristic curve (AUROC) were also computed. RESULTS: We have found genetic variants of rs5749482 (TIMP-3), rs11200638 (HTRA1), rs769449 (APOE) and rs6795735 (ADAMTS9) to be associated with AMD, concomitant with significant alterations of studied proteins levels. Analysis also revealed that the genetic interaction between APOE-HTRA1 genotypes and changes in LIPC levels (>6 pg/ug) by one unit change in SNP, play a crucial role in AMD. LR model suggested that the seven factors (including both genetic and environmental) can be utilized to predict the AMD cases with 88% efficacy and 95.6% AUROC. CONCLUSION: Results suggest that diagnostic and therapeutic strategy for Indian AMD must include estimation of genetic interaction and concomitant changes in expression levels of proteins under influence of environmental factors.

A prospective randomised control trial to compare the perioperative outcomes and ergonomic challenges between triangular versus midline port placement in total extra-peritoneal repair of uncomplicated unilateral inguinal hernia.

BACKGROUND: Routine TEP technique requires three skin incisions for placement of three trocars in the midline. Otherwise, this can be done by three-port triangular technique or two-hand technique. This study reports a randomised trial of perioperative outcomes and ergonomics characteristics of this procedure using two different techniques of port insertion. METHODS: N = 28 patients were randomised into two groups for triangular three-port (TTEP) versus midline three-port TEP (MTEP) hernioplasty after informed written consent in Department of Surgery, King George's Medical University UP between September 2016 and September 2017 after institutional ethical approval. Patient-related outcomes in terms of quality of life (QOL) and ergonomic evaluation of the technique were compared in double-blinded fashion. RESULTS: Postoperative pain score at 24 h post surgery (5.1 ± 0.6; 95% CI 4.9-5.3 vs. 4.8 ± 0.4; 95% CI 4.6-4.9) differed, while hospital stay, time to return to routine work, tolerance to oral feeds and intraoperative complications occurrence (OR 2.1; 95% CI 0.2-24.3) were comparable in both groups. Time to return to office work (5.5 ± 0.5; 95% CI 5.4-5.7 vs. 4.0 ± 0.8; 95% CI 3.7-4.3) and immediate postoperative sensation of mesh and pain score were significantly higher in MTEP compared to TTEP. Ergonomic parameters including visualization of landmark score, spreading of mesh score and total surgeon satisfaction score (TTEP 8.4 ± 0.7; 95% CI 8.1-8.6 vs. MTEP 7.0 ± 0.8; 95% CI 6.7-7.3), mental effort quotient (SMEQ score: TTEP 50.6 ± 12.7; 95% CI 45.9-55.3 vs. MTEP 70.8 ± 12.6: 95% CI 66.1-75.4) and physical effort quotient (LEDQ scores in wrist, hand, arm and shoulders) were also superior in triangular technique of port placement. CONCLUSION: Triangular three-port TEP hernioplasty is ergonomically feasible and enables a surgeon to perform surgery safely using basic principles of laparoscopy.

Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized with progressive muscle atrophy. We have attempted to establish the link between angiogenesis and cellular survival in the pathogenesis of ALS by compiling evidence described in various scientific reports. The phenotypes of human ALS have earlier been captured in the mutant SOD1 mice as well as by targeted deletion of the hypoxia response element (HRE) from the promoter of the mouse gene for vascular endothelial growth factor (VEGF). Indirect evidence shows that angiogenesis can help prevent oxidative stress, and hence, enhance cell survival. VEGF and angiogenin chiefly regulate the process of angiogenesis. Transactive response DNA-binding protein 43 (TDP-43) is usually found inside the nucleus, but in large number of cases of ALS, it accumulates in the cytoplasm (TDP-43 proteinopathy). Interestingly, TDP-43 proteinopathy is found to be aggravated in the presence of the OPTN mutation, which is the genetic factor that is responsible for such accumulation. Interaction of TDP-43 with progranulin can further affect the angiogenesis in ALS patients by regulating activity of VEGF receptors, but conclusive evidence is needed to establish its role in pathogenesis of ALS. Certain mutations in UBQLN2 and UBQLN4 indicate that ubiquitination has a role in ALS pathobiology, but its link to angiogenesis has not been adequately studied. Recent studies have shown that several mutations in RNA-binding proteins (RBPs) can also cause ALS. Conclusively, in this review, we have attempted to argue the role of angiogenesis in enhanced ALS survival rate is probably regulated with the activation of NF-κß. Additionally, interaction between OPTN and TDP-43 can also impact the transcription of various angiogenic molecules. Whether targeting angiogenic substances or TDP-43 can provide clues about extending ALS survival rate, in combination with current treatments, can only be evaluated after additional studies.

Malignancy prediction among tissues from Oral SCC patients including neck invasions: a 1H HRMAS NMR based metabolomic study.

INTRODUCTION: Oral cancer is a sixth commonly occurring cancer globally. The use of tobacco and alcohol consumption are being considered as the major risk factors for oral cancer. The metabolic profiling of tissue specimens for developing carcinogenic perturbations will allow better prognosis. OBJECTIVES: To profile and generate precise 1H HRMAS NMR spectral and quantitative statistical models of oral squamous cell carcinoma (OSCC) in tissue specimens including tumor, bed, margin and facial muscles. To apply the model in blinded prediction of malignancy among oral and neck tissues in an unknown set of patients suffering from OSCC along with neck invasion. METHODS: Statistical models of 1H HRMAS NMR spectral data on 180 tissues comprising tumor, margin and bed from 43 OSCC patients were performed. The combined metabolites, lipids spectral intensity and concentration-based malignancy prediction models were proposed. Further, 64 tissue specimens from twelve patients, including neck invasions, were tested for malignancy in a blinded manner. RESULTS: Forty-eight metabolites including lipids have been quantified in tumor and adjacent tissues. All metabolites other than lipids were found to be upregulated in malignant tissues except for ambiguous glucose. All of three prediction models have successfully identified malignancy status among blinded set of 64 tissues from 12 OSCC patients with an accuracy of above 90%. CONCLUSION: The efficiency of the models in malignancy prediction based on tumor induced metabolic perturbations supported by histopathological validation may revolutionize the OSCC assessment. Further, the results may enable machine learning to trace tumor induced altered metabolic pathways for better pattern recognition. Thus, it complements the newly developed REIMS-MS iKnife real time precession during surgery.

Effectiveness of Yoga as the Public Health Intervention Module in the Management of Diabetes and Diabetes Associated Dementia in South East Asia: A Narrative Review.

BACKGROUND: Diabetes mellitus (DM) is widely spread in South Asian (ASEAN) and Indian sub-continent. The increasing healthcare costs of DM can be prevented in the developing world by improved public healthcare interventions. Modifiable risk factors of DM like sedentary lifestyle, obesity, and stressful conditions are associated with its progression; however, the epidemiological data collected by Public Institutions are limited. SUMMARY: A review of published literature describing geographic distribution of DM and associated dementia in South Asian region, particularly India, was conducted with the purpose of assessing the feasibility and challenges associated with the Yoga-based risk reduction. PubMed and Google Scholar databases were searched for DM and dementia-related articles by using a combination of keywords: Diabetes, Diabetes related Dementia Southeast Asia, Pre-diabetes, Yoga, lifestyle modification, Dementia and Exercise. The epidemiological data generated from these diseases have not prompted to any major public health policies. Yoga can be a cost-effective intervention for the prevention of Type 2 DM (T2DM) and its associated cognitive decline when detected early. If nationwide intervention of Yoga is brought about by the state, its integration in health care will become more meaningful and acceptable. Key Message: Studies suggest that Yoga and change in lifestyle can modify the health risks associated with T2DM and associated dementia if it is mainstreamed with the public health initiative of Ayushman Bharat scheme.

Identifying putative cerebrospinal fluid biomarkers of amyotrophic lateral sclerosis in a north Indian population.

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.

Transfascial suture versus tack fixation of mesh in totally extraperitoneal repair of inguinal hernia: A prospective comparative study.

Purpose: Among laparoscopic surgeries in inguinal hernias, totally extraperitoneal (TEP) repair has demonstrated favourable results in reduction of post-operative pain and mean operative times with early return to physical activity. We have done a prospective comparative study on two different techniques of mesh fixation, i.e., transfascial suture and tack fixation. Materials and Methods: It was a prospective, non-randomised comparative study done on inguinal hernia patients operated by TEP repair from October 2014 to September 2016. These data were compared in two techniques of mesh fixation (tack and transfascial sutures) in terms of post-operative complications, pain scores by visual analogue scale (VAS) and cost analysis of the procedure. Results: Our study on 69 total patients (44 tack fixation and 25 suture fixation group) revealed that mean VAS scores for post-operative pain were not having any statistically significant difference in the tack group versus suture group (2.42 ± 0.24 vs. 2.2 ± 0.24) at 24 h, but VAS scores in the follow-up period at 1 week, 1 month, 3 months and 6 months were 1.14 ± 0.33 versus 0.67 ± 0.27; 0.78 ± 0.24 versus 0.07 ± 0.06; 0.42 ± 0.17 versus 0.07 ± 0.06 and 0.5 ± 0.11 versus 0.07 ± 0.06, respectively, which showed significant difference at 1 and 3 months, suggesting less pain in the suture group. No significant difference was noted in other post-operative complications. Conclusion: Transfascial suture fixation of mesh in TEP repair of inguinal hernia can be a cost-effective procedure with a comparable safety profile as compared to tack fixation.

Repurposing Pathogenic Variants of DMD Gene and its Isoforms for DMD Exon Skipping Intervention.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a progressive, fatal neuromuscular disorder caused by mutations in the DMD gene. Emerging antisense oligomer based exon skipping therapy provides hope for the restoration of the reading frame. OBJECTIVES: Population-based DMD mutation database may enable exon skipping to be used for the benefit of patients. Hence, we planned this study to identify DMD gene variants in North Indian DMD cases. METHODS: A total of 100 DMD cases were recruited and Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to obtain the deletion and duplication profile. RESULTS: Copy number variations (deletion/duplication) were found in 80.85% of unrelated DMD cases. Sixty-eight percent of cases were found to have variations in the distal hotspot region (Exon 45-55) of the DMD gene. Exon 44/45 variations were found to be the most prominent among single exon variations, whereas exon 49/50 was found to be the most frequently mutated locations in single/multiple exon variations. As per Leiden databases, 86.84% cases harboured out-of-frame mutations. Domain wise investigation revealed that 68% of mutations were localized in the region of spectrin repeats. Dp140 isoform was predicted to be absent in 62/76 (81.57%) cases. A total of 45/80 (56.25%) and 23/80 (28.70%) DMD subjects were predicted to be amenable to exon 51 and exon 45 skipping trials, respectively. CONCLUSION: A major proportion of DMD subjects (80%) could be diagnosed by the MLPA technique. The data generated from our study may be beneficial for strengthening of mutation database in the North Indian population.

Early Life Pb Exposure and its Effect on Later Life Retinal Degeneration.

The study presents the longitudinal effect of early life lead exposure on retinal ischemia. Swiss albino mice were exposed to lead acetate at two different timepoints viz. postnatal day 1-20 and at 7th week of age. These mice were then followed till 10 week of age and subjected to retinal ischemia. Retinal ischemia was induced using pterygopalatine artery ligation. The effect of prior lead exposure on ischemic insult was determined using various histological and molecular parameters. Although toxic effects of Pb are well reported, but the results in this study showed not much significant effect of early life Pb exposure on later life retinal degeneration. While retinal thickness was decreased in surgery group and 7th week Pb exposed group, PND Pb exposed mice showed retinal thickness comparable to normal control. There was no difference in TUNEL positive cells in Pb exposed group when compared to surgery group. The molecular studies revealed overexpression of BDNF and GFAP in PND Pb exposed mice reflecting more injury and inflammation. The combined results revealed that Pb exposure have mild effect on overall susceptibility to retinal damage in later life. The Pb may exert its toxic effects at longer duration and thus the toxic effects may be mapped at longer timepoints. The study provides a new dimension to the already well known toxic effects of lead which needs to be further explored. J. Cell. Biochem. 118: 3213-3224, 2017. © 2017 Wiley Periodicals, Inc.

Alteration of Neurotrophic Factors After Transplantation of Bone Marrow Derived Lin-ve Stem Cell in NMDA-Induced Mouse Model of Retinal Degeneration.

Retinal ganglion cell layer (RGCs) is one of the important layers of retina, depleted in Glaucoma. Loss of RGC neurons is a major cellular mechanism involved in its pathogenesis resulting in severe vision loss. Stem cell therapy has emerged as a potential strategy to arrest the apoptotic loss of RGCs and also replace the degenerative cells in damaged retina. Here, we have investigated the incorporation and survival of mouse bone marrow derived Lin-ve stem cells in N-methyl-d-aspartate (NMDA)-induced mouse model of retinal degeneration. Two days after intravitreal injection of NMDA (100 mM) showed significant decrease in ganglion cell number and increase in TUNEL positive apoptotic cells in retinal layers. The injury was further characterized by immunohistochemical expression of Brn3b, GFAP, Bcl2, pCREB, CNTF, GDNF, and BDNF in retinal layers. Lin-ve cells (100,000 dose) were intravitreally transplanted after 2 days of injury and evaluated after 7, 14, and 21 days of transplantation. Transplanted cells were found to have migrated from intravitreal space and incorporated into injured retina at 7, 14, and 21 days post-transplantation. At 21 days Brn3b, CNTF, and BDNF expression was found to be upregulated whereas GDNF was downregulated when compared to respective injury time points. Molecular data showed decrease in the expression of Brn3b, BDNF, CNTF, and GDNF post transplantation when compared with injury groups. This study reveals that Lin-ve stem cells may exert neuroprotective effect in damaged retina mediated by participation of neurotrophic factors induced by stem cell transplantation at the site of injury. J. Cell. Biochem. 118: 1699-1711, 2017. © 2016 Wiley Periodicals, Inc.

Serum Levels of TIMP-3, LIPC, IER3, and SLC16A8 in CFH-Negative AMD Cases.

AMD is a complex eye disease predominantly occurring in aged population. Till now about 53 genetic loci have been found to be associated with the AMD pathology. AMD pathogenesis is being increasingly known to progress through mechanisms independent of the CFH mediated pathway. Therefore, our aim for current study was to examine the genes by analyzing their expression levels in AMD. We recruited about 50 AMD and same number of age matched controls. We analyzed the CFH duplication and deletion by multiplex ligation probe amplification (MLPA) and found no duplication and deletion in CFH gene in AMD patients. We also estimated the IER-3, SLC16A8, LIPC, and TIMP-3 expression levels in both CFH-negative AMD cases (i.e. no duplication and deletion in CFH gene) besides examining these in AMD and controls. We found that the expression level of LIPC, SLC16A8, and TIMP-3 was significantly associated with AMD pathology in both groups (LIPC: P = 0.008, SLC16A8: P < 0.001, TIMP-3: P < 0.001, respectively). However, we did not find any significant difference in IER-3 levels in AMD and controls. Therefore, the evidence from current study, suggests that AMD pathology may be mediated through mechanistic pathways linked to other genetic loci. J. Cell. Biochem. 118: 2087-2095, 2017. © 2016 Wiley Periodicals, Inc.

Transplantation of lineage-negative stem cells in pterygopalatine artery ligation induced retinal ischemia-reperfusion injury in mice.

Retinal ischemia is a condition associated with retinal degenerative diseases such as glaucoma, diabetic retinopathy, and other optic neuropathies, leading to visual impairment and blindness worldwide. Currently, there is no therapy available for ischemic retinopathies. Therefore, the aim of this study was to test a murine model of pterygopalatine artery ligation-induced retinal injury for transplantation of mouse bone marrow-derived lineage-negative (lin-ve) stem cells. The mouse external carotid artery and pterygopalatine artery were ligated for 3.5 h followed by reperfusion. The model was validated through fundus fluorescein angiography, laser Doppler and FITC dextran perfusion in whole-mounts. Lin-ve stem cells isolated from mouse bone marrow were transplanted through tail-vein, which showed migration to retina leading to decrease in GFAP expression. The neurotrophic factors such as BDNF and FGF2 showed enhanced expression in the retina. The functional analysis with electroretinogram did not demonstrate any significant changes before or after injury or stem cell transplantation. This study shows a neuroprotective potential in lin-ve stem cells in the retinal ischemia induced by pterygopalatine artery ligation and presents a practical model for validating therapies for ischemic disorders of the retina in future.

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment.

AIM OF THE STUDY: Vitamin D receptor (VDR) expression and serum vitamin D scores in oral premalignant lesions and oral cancer have not been widely analyzed. The role of vitamin D supplementation in advanced oral cancer for improving quality of life (QOL) is also a matter of research. MATERIAL AND METHODS: Vitamin D receptor expression and vitamin D scores were analyzed in normal oral mucosa (n = 95), leukoplakia (n = 23) and oral cancer (n = 87). 45 patients with advanced oral cancer subjected to chemoradiation were evaluated for the effect of vitamin D supplementation on most observable QOL parameters such as oral mucositis, swallowing performance and overall QOL. RESULTS: Vitamin D receptor expression was increased in oral neoplastic lesions. Vitamin D scores were significantly lower in cases compared to healthy controls (p = 0.002). Vitamin D supplementation significantly reduced the therapy-related toxicities in advanced cancer, thus reducing morbidity and improving QOL. CONCLUSIONS: Vitamin D receptor expression is increased in premalignant lesions and oral cancer. Vitamin D insufficiency and deficiency are prevalent in patients with oral neoplastic lesions. Vitamin D supplementation has a role in reducing treatment-related toxicities, especially in advanced cancer.

Preserving neural retina through re-emerging herbal interventions.

Eye related diseases such as glaucoma, diabetic retinopathy, cataract, conjunctivitis are very common worldwide. With the current scenario India will be among the top five countries in the number of glaucoma cases. Limited discovery of successful drugs for the treatment of such diseases led scientists to look towards the use of conventional sources for treatment. Herbal extracts from Ayurveda have remained an important part of treatment regime in many parts of world even today. For this reason, local herbs possessing curative properties are still being used by local inhabitants due to its anti-inflammatory and antioxidant properties. Because retinal damage involves alterations in oxidative enzymes, blood flow changes and increase in apoptotic signals, herbal extracts are being tested for their ability to moderate antioxidant machinery and trigger neuroprotective pathways. The present review summarizes some of such herbal extracts which have been tested for their neuroprotective role in eye related diseases. The active components that exert neuroprotective effects have also been discussed along with possible mechanisms of action.

Cytoskeleton dynamics in the retina.

BACKGROUND: Cytoskeleton is one of the essential forms of protein, important in the existence of both eukaryotic as well as prokaryotic cells. Its transformation plays a vital role in cell division and intracellular transportation by facilitating intracellular vesicular traffic. Among the various tissue types in the body, the neural tissue exhibits the maximum heterogeneity, and hence the role of cytoskeleton at both developmental and functional levels becomes paramount. Cytoskeleton dynamics have been established in the neural physiology, but only at the level of axonal development and growth. Retina has not been adequately studied in the context of cytoskeletal proteins. METHODS: We reviewed the last 10 years of literature with reference to the development, growth, degeneration, and regeneration of the retina and the role of cytoskeleton in each aspect. We have focused on various changes that the retina undergoes at the cytosolic and cytoskeletal levels in the course of degeneration as well as regeneration. FINDINGS: For this review, we compiled research articles pertaining to the role of cytoskeletal and other associated proteins involved in development of retina, which used various animal models. The effect of SNPs in the cytoskeletal proteins and their impact in retinal degeneration is also discussed. CONCLUSION: Studies describing the role of cytoskeleton in the anatomy and physiology of retina and its layers, although they are few, collectively provide an opportunity to understand retinal development in the context of cytoskeleton dynamics.

Does toll-like receptor-3 (TLR-3) have any role in Indian AMD phenotype?

Age-related macular degeneration (AMD) is a devastating disease that results in irreversible central vision loss. TLRs signaling pathway has been found to play an important role in AMD pathogenesis as evidenced by several studies. The objective of the study was to determine the single nucleotide polymorphism (SNP) changes in TLR3 in North Indian AMD patients. We recruited 176 patients comprising 115 AMD patients and 61 controls. Real time PCR was used to evaluate the SNP changes at rs3775291 locus. Pearson's χ(2) test was used evaluate association between various groups. No significant association in genotype and allele frequency was found in AMD patients as compared to control. The results suggest that AMD pathology in North Indian AMD patients is not affected by TLR3 signaling but it could be influenced by other genetic or environmental factors unique to North India.

Using current data to define new approach in age related macular degeneration: need to accelerate translational research.

Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease.