Basic Research

S. No. Project Principal Investigators Department Duration
1 Identification of biomarkers for risk prediction and disease progression in Retinopathy of Prematurity: a potentially blinding neonatal disorder Department of Biotechnology, India Dr. Inderjeet Kaur 2012 -2015
2 Derivation of retinal  neurons from ciliary pigmented epithelium of the human eye Dr Indumathi Marriappan Science & Engineering Research Board ( SERB), India 2010-2013
3 Investigation of Epidemic Keratoconjuctivities in Orissa and Andhra Pradesh: Epidemiological profile, clinical spectrum and molecular characterization of causative agents Dr Savitri Sharma

Department of Biotechnology,

India
2010-2013
4 Control of Focusing and eye alignment during Human visual development Dr Shrikant Bharadwaj Department of Science and Technology, India 2012 -2015
5 Molecular mechanism of pathogenesis of glaucoma caused by mutation in optineurin Dr Subhabrata Chakrabarti Department of Biotechnology, India 2010-2014
6 Establishing a risk assessment chip for the eye disease age related macular degeneration Dr Subhabrata Chakrabarti Department of Biotechnology, India 2009-2013
7 National Retinoblastoma Registry Dr Swati Kaliki Indian Council of Medical Research, India 2012 - 2014
8 Genetic and phenotypic comparison of primary congenital glaucoma in India and Brazil Dr. Subhabrata Chakrabarti Department of Science and Technology 2009-2013
9 Genetic comparison of primary congenital glaucoma in India and Tunisia - Understanding the possible founder effects Dr. Subhabrata Chakrabarti Department of Science and Technology, India 2009-2013
10 Optics of the growing crystalline lens Dr V S Sangwan NIH 2012 onwards
11 Genetic Studies on Stevens Johnson Syndrome Dr Chitra Kannabiran ICMR 2012-2015
12 Development of a synthetic biodegradable cell carrier membrane for the transplantation of cultured cells or freshly excised autologous tissue (limbal segments or oral mucosa) for diseases of the cornea Prof. D Balasubramanian/ Dr V S Sangwan Wellcome Trust 2010 onwards
13 Centre of Excellence (CoE)

Prof D Balasubramanian/ Dr Subhabrata Chakrabarthi/ Dr Chitra Kannabiran/ Dr Indumathi Marriappan

Department of Biotechnology, India 2013 onwards
Identification Of Biomarkers For Risk Prediction And Disease Progression In Retinopathy Of Prematurity (ROP): A Potentially Blinding Neonatal Disorder

Investigators: Inderjeet Kaur, Sonika Rathi, Subhadra Jalali, T Ramakrishna Murthy, Ramesha Kekunaya, Sonika Rathi, Shahana, Hameed, Subhabrata Chakrabarti, Ch Mohan Rao

Support: Department of Biotechnology, India

Retinopathy of prematurity (ROP) is a self-limiting, vascular vitreoretinopathy that affects premature infants with short gestational age and low birth-weight and remains a leading cause (5-8%) of vision impairment and blindness in children There is a great need for a comprehensive research work on neovascular eye disease which might result in identifying predictive markers for severe ROP and anti-angiogenic approaches that will arrest the development of ROP by specifically targeting the involved molecular mediators. The present study aims to dissect the underlying molecular mechanism in ROP through a combination of molecular genetics, transcriptomics and proteomics based approaches, which would then be assessed with clinical parameters to understand the genotype-phenotype correlation. Proteomic analysis of vitreous humor and plasma samples of ROP patients is being undertaken at the Centre for Cellular and Molecular Biology (CCMB), Hyderabad. The expected outcome of this research would be the identification of biomarkers for ROP that could be eventually helpful in developing a diagnostic test for risk prediction. Timely detection and molecular diagnosis of ROP would also help in better prognosis of the disease and avoid the complete visual loss among the preterm babies.

Derivation Of Retinal Neurons From Ciliary Pigmented Epithelium Of The Human Eye

Investigators: Indumathi Mariappan

Support: Department of Science & Technology, India

The ciliary margin zone is known to harbor retinal stem cells in lower vertebrates and plays an active role in the regeneration of the adult retina. Proliferating stem-like cells were also reported in the ciliary-pigmented epithelium (CPE) of higher mammals like the mouse and rat. These CPE cells were shown to differentiate into RPE cells and retinal neurons, including the photoreceptor cells. This study aims to culture and characterize the human ciliary-pigmented epithelium derived retinal stem cells (RSCs), using cadaveric donor eyeballs collected from the eye bank as the tissue source and to identify suitable culture conditions for the differentiation of RSCs into different retinal cell types. We have found that a subset of pigmented cells of the CPE layer has retinal progenitor properties and can proliferate in culture. We have established both adherent and sphere cultures of CPE cells and found that the CPE cells share a common gene expression signature with the neuro-retinal and RPE cells and a rare population of CPE cells retains the potential to proliferate and differentiate into retinal cells. However, some retinal transcription factors were found to be abnormally localized to different sub-cellular compartments which might contribute to aberrant downstream signaling and limited retinal potential of CPE cells.

Investigation Of Epidemic Keratoconjunctivitis In Odisha And Andhra Pradesh: Epidemiological Profile, Clinical Spectrum And Molecular Characterization Of Causative Agents

Investigators: Savitri Sharma, Sujata Das, Srikant K Sahu, Somasheila Murthy, BNR Subudhi2

Support: Department of Biotechnology, India

Epidemic keratoconjunctivitis (EKC) is a worldwide problemcausing significant and, sometimes, lasting morbidity. Humanadenoviruses (HAdVs) HAdV-D8, -D19, and -D37 are believed to be the most common pathogens causing EKC. It is only recently that another organism has come to be associatedwith EKC. We observed a seasonal outbreak of Epidemic Keratoconjunctivitis (EKC) that clinically mimicked viral EKC,but was proven to be a microsporidial infection by laboratory investigations. Though EKC is usually caused by adenovirus type8, 19 and 37, the association of microsporidia with EKC has not been studied so far. In this study, we plan to investigate the seasonal EKC that occurs in Odisha and other parts of the country year after year, and to characterize the adenovirus and microsporidia isolated from the environment as well as from patients with epidemic keratoconjunctivitis. The study will determine the clinical spectrum of the disease in patients and examine the interaction between the two organisms in the environment and in the patients, if any. Samples from over 300 patients and controls have been tested. Samples have also been collected from water bodies in villages around Bhubaneswar and are being processed.

Footnote

  1. Institute of Life Sciences, Bhubaneswar
  2. MKCG Medical College, Berhampur, Odisha
Molecular Mechanism Of Pathogenesis Of Glaucoma Caused By Mutation In Optineurin

Investigators: D Balasubramanian, Ghanshyam Swarup3, Subhabrata Chakrabarti

Support: Department of Biotechnology, India

Optineurin is a multifunctional protein involved in several functions such as vesicular trafficking from the Golgi to the plasma membrane, NF-kappaB regulation, signal transduction and gene expression. Mutations in optineurin are associated with glaucoma. However, functional alterations caused by mutations in optineurin are not known. Here, we have analyzed the role of optineurin in endocytic recycling and the effect of the severe disease-causing E50K mutant on this process. Our results show that the knockdown of optineurin impairs trafficking of transferrin receptor to the juxtanuclear region. Studies using cell lines transfected with the wild type and the E50K mutant cDNAs show that E50K impairs endocytic recycling of transferrin receptor as shown by enlarged recycling endosomes, slower dynamics of E50K vesicles and decreased transferrin uptake by the E50K-expressing cells. This impaired trafficking by the E50K mutant requires the function of its ubiquitin-binding domain. Compared to wild type optineurin, the E50K optineurin shows enhanced interaction and colocalization with transferrin receptor and Rab8. The velocity of Rab8 vesicles is reduced by co-expression of the E50K mutant. These results suggest that the E50K impairs trafficking at the recycling endosomes due to altered interactions with Rab8 and transferrin receptor. These results have implications for the pathogenesis of glaucoma caused by the E50K mutation because endocytic recycling is vital for maintaining homeostasis.

Footnote

  1. National Institute of Biomedical Genomics, Kalyani, West Bengal,
  2. University of New South Wales, Australia,
  3. Centre for Cellular and Molecular Biology, Hyderabad
Genetic And Phenotypic Comparison Of Primary Congenital Glaucoma In India And Brazil

Investigators: Subhabrata Chakrabarti, Anil K Mandal, Ivan M Tavares,1, Jose P C Vasconcellos,2 , Monica Mello2,

Support: Department of Science and Technology, India (Indo-Brazil collaborative program)

Primary congenital glaucoma (PCG) is largely attributed to mutations in the CYP1B1 gene resulting in irreversible blindness across children in the developing world. While the mutation frequencies widely vary across populations, there are subtle commonalities with respect to the prevalent mutation that occurs on a uniform genetic signature (haplotype). We looked for clinical indicators for common and local mutations in CYP1B1 across PCG patients in India and Brazil for undertaking a genotype-phenotype correlation. The initial results indicate that gender, consanguinity and presenting cup to disk ratios (CDR) among the Brazilian patients were strongly associated with the presence of a mutation. On the other hand, presenting IOP, CDR and family history conferred the maximum risk in PCG patients harboring a mutation in the Indian patients.

Genetic Comparison Of Primary Congenital Glaucoma In India And Tunisia – Understanding The Possible Founder Effects

Investigators: Subhabrata Chakrabarti, Anil K Mandal, Guemira Fethi5, E A Mhd Ali6 , Douik Hayet6, G Abderraouf 7, Harzallah Latifa7, Jihene Bouassida7

Support: Department of Science and Technology, India (Indo-Tunisia collaborative program)

Primary congenital glaucoma (PCG), attributed to mutations in the CYP1B1 gene, affects different populations worldwide. These mutations exhibit a strong geographical clustering, based on a uniform haplotype background, as evidenced from the mutation spectrum among PCG patients in Morocco, Saudi Arabia and India. So far, there are no reports on the genetics of PCG in Tunisia. In the present study, we estimated the overall mutation spectrum of CYP1B1 in Tunisia. Further, we hypothesized that common and prevalent mutations, such as G61E and 4340delG among Tunisian patients may have a strong founder effect, as seen elsewhere. The current analysis addressed the similarities and dissimilarities in the genetic basis of PCG in Tunisia and India along with their origin and migration. We also established the founder effect for the G61E mutation with Saudi Arabians and Indians and 4340delG with other populations (Brazilians) and its diversification worldwide.

Footnote

  1. Vision Institute, Federal University of Sao Paolo, Brazil
  2. Campinas State University, Sao Paolo, Brazil
  3. University of Heidelberg, Manheim, Germany
  4. Suraj Eye Institute, Nagpur
  5. Institut Salah Azaiz, Tunis, Tunisia
  6. Service d’Ophthalmologie, Habib Thameur Hospital, Tunis, Tunisia
  7. Service de Biologie Clinique, Institut Salah Azaiz, Tunis, Tunisia
Development Of A Synthetic Bio-Degradable Cell Carrier Membrane For The Transplantation Of Cultured Cells Or Freshly Excised Autologous Tissue (Limbal Segments) For Diseases Of The Cornea

Investigators: Virender S Sangwan, D Balasubramanian, Sheila Macneil,* Indumathi Mariappan, Charanya Ramachandran

Support: Wellcome Trust, United Kingdom

When the outer epithelial layer of the cornea is damaged by chemical or fire burns, vision is compromised. In some cases, stem cell therapy can be used to generate a functional outer corneal layer to offer significant restoration of vision. The human amniotic membrane is currently the most commonly used substrate for culturing and transplanting limbal stem cells. While this procedure is successful, the study investigates whether it is possible to replace the amniotic membrane, so as to avoid viral contamination, shelf life degradation and other potential risks associated with the use of a biological material. A synthetic biodegradable polymer membrane developed by our collaborators at the University of Sheffield promises to be valuable. Our research thus far shows that the polymer scaffold, similar to the human amniotic membrane, supports sufficient stem cell growth and allows successful transfer of the cultured cells onto the wounded cornea. Following the promising laboratory data and rabbit toxicity results, a pilot clinical trial to test the safety and efficacy of the polymer scaffold has been planned.

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