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«ARAVIND MEDICAL RESEARCH FOUNDATION Aravind Medical Research Foundation is recognized as Scientific and Industrial Research Organization (SIRO) by ...»

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ARAVIND MEDICAL RESEARCH FOUNDATION

Aravind Medical Research Foundation is recognized as

Scientific and Industrial Research Organization (SIRO) by

the Department of Scientific and Industrial Research (DSIR)

MISSION

To eliminate needless blindness by providing

evidence through research and evolving methods

to translate existing evidence and knowledge into

effective action.

RESEARCH IN OPHTHALMIC SCIENCES

Dr. G. Venkataswamy Eye Research Institute Annual Report 2015 - 2016

ARAVIND MEDICAL RESEARCH FOUNDATION

Much has been done, but much remains to be done… we look to the future with renewed strength to continue the mission of providing quality eye care and hope that some of what we have learned will be useful to other eye care workers around the world.

RESEARCH IN OPHTHALMIC SCIENCES

Dr. G. Venkataswamy Eye Research Institute Annual Report 2015 - 2016

ARAVIND MEDICAL RESEARCH FOUNDATION

BOARD OF MANAGEMENT

MR. R.D. THULASIRAJ, DR. P. NAMPERUMALSAMY, DR. G. NATCHIAR, MS, DO ER. G. SRINIVASAN, BE, MS MBA MS, FAMS DR. R. KIM, DO., DNB DR. S.R. KRISHNADAS, DR.N.VENKATESH PRAJNA DR. S. ARAVIND, MS, MBA DO., DNB., FRCophth DO., DNB

RESEARCH ADVISORY COMMITTEE INSTITUTIONAL ETHICS COMMITTEE (IEC)

Chairman Chairman DR. P. NAMPERUMALSAMY PROF. R. VENKATARATNAM M.A., PH.D Chairman – Emeritus Senior Prof.of Sociology (Retired) Aravind Eye Care System Madurai Kamaraj University, Madurai 1, Anna Nagar, Madurai - 625 020 Member-Secretary Member-Secretary DR. LALITHA PRAJNA MD, DNB PROF. K. DHARMALINGAM Chief Microbiologist Director - Research Aravind Eye Hospital, Madurai Aravind Medical Research Foundation Members 1, Anna Nagar, Madurai - 625020 DR. C. SRINIVASAN M.SC.,PH.D Members UGC Emeritus Professor PROF. VR. MUTHUKKARUPPAN New No. 2/249 (Old No 2/172) Advisor-Research 7th

–  –  –

Aravind Medical Research Foundation, the research wing of Aravind Eye &DUH 6\VWHP $(&6 LV FRPPLWWHG WR ¿QGLQJ RXW WKH URRW FDXVH RI YDULRXV sight threatening diseases prevalent in the country such as Glaucoma, Diabetic Retinopathy, Age-related Macular Degeneration and other eye

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at large and especially when this happens in the realm of healthcare, it results in a positive impact on the lives of many individuals. Studies at the institute have thrown light into the pathogenesis of many of ophthalmic

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scientists, made possible in the unique situation of Aravind that its facilities

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a larger community, which can happen only through this collaboration. This collaboration has also resulted in the establishment a state-of-the-art Genetic Testing Centre for Retinoblastoma at AECS.

Of late, the institute has been focusing on the proteomics of eye diseases mainly Fungal Keratitis, Diabetic Retinopathy and Glaucoma. High throughput proteomics approaches are being

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Continued growth of any research organization depends on the excellence of the core group of scientists and their commitment to research and education. Aravind Medical Research Foundation is fortunate to have a dedicated band of scientists who with their knowledge and expertise in relevant

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Ramprasad will be concentrating on cell signalling in fungal keratitis, and micro RNAs in Diabetic Retinopathy. Dr. Rabbind Singh will be focusing on various cancers such as Uveal Melanoma. His expertise in fungal and microbial systems as well as in cancer biology will augment the institute’s research capabilities. With the new faculty in place, AMRF is looking forward to intensifying research

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Being a research organization, educational activities such as Ph.D. programmes, symposia, workshops and courses are being conducted regularly to keep the staff, students and research

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translational research capacities.

Dr. P. NamperumalsamyPresident, AMRFINTRODUCTION

Research focus of AMRF continues to be understanding of ocular diseases. Elucidation of the mechanism as well as factors associated with disease phenotype are examined in detail. With the new faculties AMRF hopefully achieve some of the objectives in the future.





Whole genome analysis and functional genomics of eye diseases are the focus areas being pursued in AMRF by the genetics and bioinformatics groups. They work on diseases such as Glaucoma, Macular Corneal Dystrophies, Retinitis Pigmentosa and Retinoblastoma and actively pursue the leads they have obtained in the previous years. They have found some novel mutations in genes involved in some of the diseases and also examined additional mutations that have role to play in the diseases. A computational platform for mutation screening was developed in collaboration with the bioinformatics group. Analysis of

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disease, which in the long run allow the elucidation of the mechanism underlying the disease.

Bioinformatics group actively collaborate with the genetics group in analyzing the NGS data using the in- house developed pipelines.

Stem cell biology is having an expanding role in understanding the disease mechanisms and development of alternate strategies for treatment. Characterization and use of corneal epithelial stem cells are the focus of the group working on this aspect. This group is also analyzing the regulatory role of miRNA in stem cell differentiation.

Ocular microbiology and proteomics groups studies infection biology with special reference to bacterial and fungal keratitis. Role of autophagy in bacterial clearance in Pseudomonas keratitis has been the focus of microbiology group and recently they have started using an animal model of bacterial keratitis to better understand the persistence mechanism. Apart from analyzing fungal

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using serum and circulating micro vesicles.

Macular pigment density could be an indicator of Age Related Macular Degeneration that can be used as a predictor of AMD risk and this information has potential clinical use. Apart from this study, the ocular pharmacology group also studies the signaling in trabecular meshwork and its role in development of glaucoma with an objective to improve the management of Glaucoma.

Prof. K. DharmalingamDirector - ResearchMOLECULAR GENETICS

The most common eye disorders in Indian population are cataract, diabetic retinopathy, glaucoma, corneal and retinal dystrophies. The primary focus of the department is to identify putative genetic markers for diagnosis and genetic counselling in these eye diseases. The department of molecular genetics has given priority to study genetics of Primary Angle Closure Glaucoma (PACG) and

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patients. The lab is also interested in studying the role of SIX6 gene in the pathogenesis of primary open angle glaucoma. Newer methods were developed for the genetic analysis of retinoblastoma patients. Mutational spectrum of RB1 gene was further expanded with the analysis of promoter methylation. The next generation sequencing platform Illumina Miseq was established this year which enhances the understanding on the pathogenesis of retinoblastoma.

Molecular Genetics of Macular Corneal Dystrophy (MCD) in Indian population Investigators : Dr. P. Sundaresan, Dr.N.V.Prajna, Dr.V.Lumbini, Dr.K.Rohan Agashe Ph.D scholar : M.Durga Funding agency : Cornea clinic research grant - Mutt study Background Macular corneal dystrophy (MCD) is an inherited autosomal recessive disorder of keratan sulfate (KS) metabolism. It is caused by mutations in the carbohydrate sulfotransferase-6 (CHST6) gene, encoding corneal N-acetyl glucosamine-6-O-sulfotransferase (C-GlcNAc-6-ST) enzyme.

The abnormal accumulation of glycosaminoglycans (unsulfated keratan sulfates) in the stroma, Decemets membrane, endothelial cells leads to severe visual impairment. The onset usually occurs

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by an accumulation of irregular, focal, grey white deposits.

MCD is most prevalent in Iceland followed by Japan, India and Saudi Arabia. In South Indian population, the high prevalence of MCD is probably a result of high frequency of consanguineous marriages. There is a limited study from the Indian population with regard to MCD genetics.

Therefore, this study was undertaken to determine the spectrum of genetic variations in CHST6 gene and understand its role in MCD pathogenesis. In this study, 55 unrelated families (90 study subjects with and without MCD) were recruited and screened for mutations in CHST6 gene by Sanger sequencing. Out of 55 families, 30 families had consanguineous marriages, 20 families had the previous MCD case history. For this MCD study, 11 unaffected family members were also included as controls, along with 50 cataract controls.

Results & Conclusion In this study, eight different novel mutations in 8 families and two hotspot mutations (frameshift, missense) in 20 families (Figure 1 shows the typical pedigree of MCD and Figure 2 shows one of WKH KRWVSRW  IUDPHVKLIW GHOHWLRQ PXWDWLRQV LQ 0&' IDPLO\  ZHUH LGHQWL¿HG 1R PXWDWLRQ ZDV

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using bioinformatics prediction tools.

–  –  –

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closure glaucoma Investigators : Dr. P. Sundaresan, Dr. R. Krishnadas, Dr. R. Venkatesh, Dr. Kavitha Srinivasan Ph.D scholar : Roopam Duvesh Funding agency : Aravind Medical Research Foundation Introduction Glaucoma is a complex neurodegenerative disorder characterized by progressive retinal ganglion cell damage, loss of optic nerve axons and distinctive optic neuropathy. It leads to optic disc cupping

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the second most leading cause of blindness in the world following cataract. Primary angle closure glaucoma (PACG) results from an appositional contact between peripheral iris & trabecular

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This leads to an increase in intra ocular pressure (IOP) and damage to the optic nerve. According to the recently published meta-analysis by Tham et al, the global prevalence of glaucoma for population aged 40-80 years is 3.54% and the prevalence of PACG is highest in Asians (1.09%). It is genetically heterogeneous disorder with complex genetic basis affecting many individuals within a family.

7KH VLJQL¿FDQW DVVRFLDWLRQ RI 613 UV ZDV SUHYLRXVO\ UHSRUWHG LQ PCMTD1-ST18 gene with PAC/PACG group (p=0.002) in South Indian population (Duvesh et al, 2013). Recently, a genome wide association study (GWAS) was conducted across 24 countries (Asia, Australia, Europe, North- and South America) including 10,503 PACG cases and 29,567 controls to identify

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DW ¿YH QHZ JHQHWLF ORFL 7KHVH ORFL DUH DW EPDR1 rs3816415 (p = 3.49 x 10-15), CHAT rs1258267 (p= 3.73 x 10-16), GLIS3 rs736893 (p = 1.15 x 10-14), FERMT2 rs7494379 (p = 6.32 x 10-11), and rs3739821 mapping in between DPM2 and FAM102A on chromosome 9 (p = 6.77 x 10-12). Apart

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PACG (p 5 x 10-8 for each of PLEKHA7 rs11024102, COL11A1 rs3753841, and PCMTD1-ST18 rs1015213).

In collaboration with Singapore Eye Research Institute (SERI), 190 PACG cases and 288 controls were analyzed for these SNPs using Taqman allelic discrimination assay in South Indian population.

Results and conclusion +LJKO\ VLJQL¿FDQW DVVRFLDWLRQ RI 613 UV ZDV REVHUYHG LQ PCMTD1-ST18 (p=9.17E-05)

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VLJQL¿FDQW DVVRFLDWLRQ RI D QHZ ORFXV UV ZDV DOVR REVHUYHG LQ FNDC3B gene (p=0.0046).

FNDC3B is Fibronectin Type III Domain Containing 3B protein, which in earlier studies, has been associated with IOP and central corneal thickness (CCT) in primary open angle glaucoma (POAG) subjects.

Genetics and functional approaches of SIX6 gene to understand the pathogenicity of Primary open angle glaucoma Investigators : Dr. P. Sundaresan, Dr. S.R. Krishnadas, Dr. Manju Pillai, Ph.D scholar : Mohd Hussain Shah Funding agency : Aravind Medical Research Foundation Introduction Primary open angle Glaucoma is a neurodegenerative disease characterized by the progressive

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