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.

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.

Does conserved domain SOD1 mutation has any role in ALS severity and therapeutic outcome?

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative fatal disease that can affect the neurons of brain and spinal cord. ALS genetics has identified various genes to be associated with disease pathology. Oxidative stress induced bunina and lewy bodies formation can be regulated through the action of SOD1 protein. Hence, in the present study we aim to analyse the structural and functional annotation of various reported SOD1 variants throughout and their putative correlation with the location of mutation and degree of ALS severity by inferring the structural and functional alterations in different SOD1 variants. METHODS: We have retrieved around 69 SNPs of SOD1 gene from Genecards. Structural annotation of SOD1 variants were performed using SWISS Model, I-Mutant 2.0, Dynamut, ConSurf. Similarly, the functional annotation of same variants were done using SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB. Ramachandran plot was also obtained for six synonymous SNPs to compare the amino acid distribution of wild-type SOD1 (WT SOD1) protein. Frequency analysis, Chi square analysis, ANOVA and multiple regression analysis were performed to compare the structural and functional components among various groups. RESULTS AND CONCLUSION: Results showed the mutations in conserved domain of SOD1 protein are more deleterious and significantly distort the tertiary structure of protein by altering Gibb's free energy and entropy. Moreover, significant changes in SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB scores were also observed in mutations located in conserved domain of SOD1 protein. Multiple regression results were also suggesting the significant alterations in free energy and entropy for conserved domain mutations which were concordant with structural changes of SOD1 protein. Results of the study are suggesting the biological importance of location of mutation(s) which may derive the different disease phenotypes and must be dealt accordingly to provide precise therapy for ALS patients.

Genomes OnLine Database (GOLD) v.6: data updates and feature enhancements.

The Genomes Online Database (GOLD) (https://gold.jgi.doe.gov) is a manually curated data management system that catalogs sequencing projects with associated metadata from around the world. In the current version of GOLD (v.6), all projects are organized based on a four level classification system in the form of a Study, Organism (for isolates) or Biosample (for environmental samples), Sequencing Project and Analysis Project. Currently, GOLD provides information for 26 117 Studies, 239 100 Organisms, 15 887 Biosamples, 97 212 Sequencing Projects and 78 579 Analysis Projects. These are integrated with over 312 metadata fields from which 58 are controlled vocabularies with 2067 terms. The web interface facilitates submission of a diverse range of Sequencing Projects (such as isolate genome, single-cell genome, metagenome, metatranscriptome) and complex Analysis Projects (such as genome from metagenome, or combined assembly from multiple Sequencing Projects). GOLD provides a seamless interface with the Integrated Microbial Genomes (IMG) system and supports and promotes the Genomic Standards Consortium (GSC) Minimum Information standards. This paper describes the data updates and additional features added during the last two years.

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.

Distortion of the ligand molecule as a strategy for modulating binding affinity: Further studies involving complexes of jacalin with ß-substituted disaccharides.

Crystal structures of jacalin in complex with GlcNAc ß-(1,3) Gal-ß-OMe and Gal ß-(1,3) Gal-ß-OMe have been determined. The binding of the ligands to jacalin is similar to that of analogous α-substituted disaccharides. However, the ß-substituted ß-(1,3) linked disaccharides get distorted at the anomeric center and the glycosidic linkage. The distortion results in higher internal energies of the ligands leading to lower affinity to the lectin. This confirms the possibility of using ligand distortion as a strategy for modulating binding affinity. Unlike in the case of ß-substituted monosaccharides bound to jacalin, where a larger distortion at the anomeric center was observed, smaller distortions are distributed among two centers in the structures of the two ß-substituted ß-(1,3) linked disaccharides presented here. These disaccharides, like the unsubstituted and α-substituted counterparts, bind jacalin with the reducing Gal at the primary binding site, indicating that the lower binding affinity of ß-substituted disaccharides is not enough to overcome the intrinsic propensity of Gal ß-(1,3) Gal-based disaccharides to bind jacalin with the reducing sugar at the primary site. © 2017 IUBMB Life, 69(2):72-78, 2017.

Effect of linkage on the location of reducing and nonreducing sugars bound to jacalin.

The crystal structures of jacalin complexed with Gal α-(1,4) Gal and Gal α-(1,3) Gal ß-(1,4) Gal have been determined with the primary objective of exploring the effect of linkage on the location of reducing and non-reducing sugars in the extended binding site of the lectin, an issue which has not been studied thoroughly. Contrary to the earlier surmise based on simple steric considerations, the two structures demonstrate that α-linked sugars can bind to jacalin with nonreducing sugar at the primary binding site. This is made possible substantially on account of the hitherto underestimated plasticity of a non-polar region of the extended binding site. Modeling studies involving conformational search and energy minimization, along with available crystallographic and thermodynamic data, indicate a strong preference for complexation with Gal ß-(1,3) Gal with the reducing Gal at the primary site, followed by that with Gal α-(1,3) Gal, with the reducing or non-reducing Gal located at the primary binding site. This observation is in consonance with the facility of jacalin to bind mucin type O-glycans containing T-antigen core. © 2016 IUBMB Life, 68(12):971-979, 2016.

Jacalin-carbohydrate interactions: distortion of the ligand molecule as a determinant of affinity.

Jacalin is among the most thoroughly studied lectins. Its carbohydrate-binding site has also been well characterized. It has been postulated that the lower affinity of ß-galactosides for jacalin compared with α-galactosides is caused by steric interactions of the substituents in the former with the protein. This issue has been explored energetically and structurally using different appropriate carbohydrate complexes of jacalin. It turns out that the earlier postulation is not correct. The interactions of the substituent with the binding site remain essentially the same irrespective of the anomeric nature of the substitution. This is achieved through a distortion of the sugar ring in ß-galactosides. The difference in energy, and therefore in affinity, is caused by a distortion of the sugar ring in ß-galactosides. The elucidation of this unprecedented distortion of the ligand as a strategy for modulating affinity is of general interest. The crystal structures also provide a rationale for the relative affinities of the different carbohydrate ligands for jacalin.

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.

Draft Genome Sequences of Yersinia pestis Strains from the 1994 Plague Epidemic of Surat and 2002 Shimla Outbreak in India.

We report the first draft genome sequences of the strains of plague-causing bacteria, Yersinia pestis, from India. These include two strains from the Surat epidemic (1994), one strain from the Shimla outbreak (2002) and one strain from the plague surveillance activity in the Deccan plateau region (1998). Genome size for all four strains is ~4.49 million bp with 139-147 contigs. Average sequencing depth for all four genomes was 21x.

Neural stem cells-trends and advances.

For many years, accepted dogma held that brain is a static organ with no possibility of regeneration of cells in injured or diseased human brain. However, recent preclinical reports have shown regenerative potential of neural stem cells using various injury models. This has resulted in renewed hope for those suffering from spinal cord injury and neural damage. As the potential of stem cell therapy gained impact, these claims, in particular, led to widespread enthusiasm that acute and chronic injury of the nervous system would soon be a problem of the past. The devastation caused by injury or diseases of the brain and spinal cord led to wide premature acceptance that "neural stem cells (NSCs)" derived from embryonic, fetal or adult sources would soon be effective in reversing neural and spinal trauma. However, neural therapy with stem cells has not been realized to its fullest extent. Although, discrete population of regenerative stem cells seems to be present in specific areas of human brain, the function of these cells is unclear. However, similar cells in animals seem to play important role in postnatal growth as well as recovery of neural tissue from injury, anoxia, or disease.

Kawasaki Disease and Inborn Errors of Immunity: Exploring the Link and Implications.

The exact etiopathogenesis of Kawasaki disease (KD), the most common childhood vasculitis, remains unknown; however, an aberrant immune response, possibly triggered by an infectious or environmental agent in genetically predisposed children, is believed to be the underlying pathogenetic mechanism. Patients with inborn errors of immunity (IEI) are predisposed to infections that trigger immune dysregulation due to an imbalance in various arms of the immune system. KD may develop as a complication in both primary and secondary immunodeficiencies. KD may occur either at disease presentation or have a later onset in IEIs. These include X-linked agammaglobulinemia (XLA), selective IgA deficiency, transient hypogammaglobulinemia of infancy; Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES); chronic granulomatous disease (CGD), innate and intrinsic immunity defects, and autoinflammatory diseases, including PFAPA. Hitherto, the association between KD and IEI is confined to specific case reports and case series and, thus, requires extensive research for a comprehensive understanding of the underlying pathophysiological mechanisms. IEIs may serve as excellent disease models that would open new insights into the disease pathogenesis of children affected with KD. The current review highlights this critical association between KD and IEI supported by published literature.

Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study.

Age-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes 'CC' and 'GC' of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.

Genotyping of Clinical Parameters in Age-Related Macular Degeneration.

BACKGROUND: Optical coherence tomography (OCT) parameters like subretinal fluid (SRF), intra retinal fluid (IRF) and retinal detachment (RPED) etc are routinely accessed by ophthalmologists in patients with retinal complaints. Correlation of OCT findings with genotype and phenotype of AMD patients is relatively unexplored. Here, we have investigated the association of OCT parameters' with genetic variants along with protein expressions and examined their clinical relevance with AREDS (Age-Related Eye Disease Study) criteria in AMD patients. METHODS: For this study, samples were recruited from Advanced Eye Centre, PGIMER, Chandigarh, India. Case-only analysis of anonymous imaging data (OCT/Fundus) acquired during the routine clinical evaluation of patients was done to examine the OCT findings in the AMD patients. TaqMan genotyping assays were used to analyze the single nucleotide polymorphisms in these patients. ELISA (enzyme linked immunosorbent assay) was used to estimate the protein levels of these genes in serum. Information pertaining to lifestyle/habits was also collected by administering a standard questionnaire at the time of recruitment of the patients. RESULTS: Intra-retinal fluid (IRF) was associated significantly with the LIPC genotype (p=0.04). Similarly, smoking status and early AMD were also associated with the APOE genotype (p=0.03). Additionally, variants of IER-3 and SLC16A8 were also found to be associated with co-morbidities (p=0.02) and males (p=0.02), respectively. RPED has shown a significant association with AREDS criteria, which demonstrated an area under AUROC around 72%. CONCLUSION: Results of genotype-phenotype association can give a precise impression of AMD severity and can be beneficial for the early diagnosis of AMD cases.

Mechanisms of Immune Dysregulation in COVID-19 Are Different From SARS and MERS: A Perspective in Context of Kawasaki Disease and MIS-C.

Coronaviruses have led to three major outbreaks to date-Severe Acute Respiratory Syndrome (SARS; 2002), Middle East Respiratory Syndrome (MERS; 2012) and the ongoing pandemic, Coronavirus Disease (COVID-19; 2019). Coronavirus infections are usually mild in children. However, a few children with MERS had presented with a severe phenotype in the acute phase resulting in progressive pneumonic changes with increasing oxygen dependency and acute respiratory distress requiring ventilatory support. A subset of children with a history of SARS-CoV-2 infection develops a multisystem hyper-inflammatory phenotype known as Multisystem Inflammatory Syndrome in Children (MIS-C). This syndrome occurs 4-6 weeks after infection with SARS-CoV-2 and has been reported more often from areas with high community transmission. Children with MIS-C present with high fever and often have involvement of cardiovascular, gastrointestinal and hematologic systems leading to multiorgan failure. This is accompanied by elevation of pro-inflammatory cytokines such as IL-6 and IL-10. MIS-C has several similarities with Kawasaki disease (KD) considering children with both conditions present with fever, rash, conjunctival injection, mucosal symptoms and swelling of hands and feet. For reasons that are still not clear, both KD and MIS-C were not reported during the SARS-CoV and MERS-CoV outbreaks. As SARS-CoV-2 differs from SARS-CoV by 19.5% and MERS by 50% in terms of sequence identity, differences in genomic and proteomic profiles may explain the varied disease immunopathology and host responses. Left untreated, MIS-C may lead to severe abdominal pain, ventricular dysfunction and shock. Immunological investigations reveal reduced numbers of follicular B cells, increased numbers of terminally differentiated CD4+T lymphocytes, and decreased IL-17A. There is still ambiguity about the clinical and immunologic risk factors that predispose some children to development of MIS-C while sparing others. Host-pathogen interactions in SARS, MERS and COVID-19 are likely to play a crucial role in the clinical phenotypes that manifest. This narrative review focuses on the immunological basis for development of MIS-C syndrome in the ongoing SARS-CoV-2 pandemic. To the best of our knowledge, these aspects have not been reviewed before.

Yoga as a Preventive Intervention for Cardiovascular Diseases and Associated Comorbidities: Open-Label Single Arm Study.

Aim: Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD). Methods: In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological [body mass index (BMI), blood pressure, percent oxygen saturation], biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention. Results: At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group (hypertension, diabetes, underwent surgery, and CVD). Conclusion: These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD.

Sleeping pattern and activities of daily living modulate protein expression in AMD.

Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.

Serum Levels of ARMS2, COL8A1, RAD51B, and VEGF and their Correlations in Age-related Macular Degeneration.

BACKGROUND: Many factors including genetic and environmental are responsible for the incidence of Age-related Macular Degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet. OBJECTIVE: This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis. METHODS: For this case-control study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA (enzyme-linked immunosorbent assay) was used for the estimation of proteins in the serum of patients. RESULTS: ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r = 0.933, p < 0.0001), ARMS2 and RAD51B (r = 0.704, p < 0.0001), ARMS2 and VEGF (r = 0.925, p < 0.0001), COL8A1 and RAD51B (r = 0.736, p < 0.0001), COL8A1 and VEGF (r = 0.879, p < 0.0001), and RAD51B and VEGF (r = 0.691, p < 0.0001). CONCLUSION: The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.