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Ocular Research

Current activities Past activities Future trends  

Visual disability from diabetes is a significant public health problem and the need of the hour is to assess the burden of different aspects of eye problems seen in diabetes. With this in view the Ocular Research Unit at the MDRF was established in 1996 to study the retinal diseases seen in diabetes. Research undertaken at this unit covers a whole range of clinical, biochemical, genetic, epidemiological and experimental aspects of eye diseases in diabetes. Research activities include studying the prevalence and associated risk factors of DR and the intricacies of the molecular mechanisms involved in retinal neovascularisation which can pave the way for future therapeutic measures. The unit has established a cell model system with culturing facilities for retinal endothelial cells for the first time in India. Screening for different polymorphorisms and genetic markers for diabetic retinopathy are also under progress. This department has extended its research activities by starting a Ph.D programme in ophthalmology since 2003 and 3 students have successfully completed their doctoral (Ph.D) degrees with Dr.M.Rema as their mentor.

 
  Vision  
 

To determine the prevalence/incidence of diabetes related eye problems in the population and in the clinical population

To assess the impact of therapy for diabetic retinopathy and to study molecular mechanisms using post-mortem retinal endothelial cells

 
  Mission  
 

To provide excellence in diabetes related eye research by dissemination of information on the burden, cause, prevention and management of ocular problems among fellow eye researchers both within the institute and across India through research and education.

 
 

Portfolio of Current Activities of the Department

 
 

1. Population-based prospective cohort study to assess the incidence of  diabetic retinopathy in the participants of Chennai Urban Rural Epidemiology Study (CURES) Dr. M. Rema, Dr. M. Deepa, Dr .R. Pradeepa

The study aims to assess the 5-year incidence of diabetic retinopathy among participants of the CURES Eye Study. The study will help to assess the incidence and risk factors of diabetic retinopathy (DR) among type 2 diabetic subjects in Chennai. Follow-up studies on diabetic retinopathy  are necessary to collect data on progression of DR, as proliferative retinopathy poses a serious health threat to vision  that may be preventable by early diagnosis and intervention.

2. Young Diabetic Retinopathy Study (YDRS)
Dr. R. Rajalakshmi, Dr. M. Rema

The aims of the current study are:
1. To estimate the prevalence of diabetic retinopathy in young diabetic subjects in the clinic cohort.
2. To assess the incidence of diabetic retinopathy and sight threatening diabetic retinopathy (Diabetic macular edema and Proliferative Diabetic retinopathy)
3. To assess the role of risk factors in the development and progression of retinopathy.
4. To estimate the co-relation with other micro-vascular and macro-vascular complications of diabetes. 

3. Erythropoietin [friend or foe] in proliferative diabetic retinopathy
 Ms. M. Nithyakalyani, Dr. M. Rema

The aims of this study are to:

  • Investigate the levels of EPO and other angiogenic and angiostatic factors in vitreous and plasma of controls and proliferative diabetic retinopathy patients?
  • Observe retinal tissue morphology in PDR samples compared to controls and to find out the expression pattern of EPO /EPOR, VEGF/VEGFR and PEDF in the human retinal tissue.
  • Evaluate effects of exogenous EPO administration on HRECs (Human retinal Endothelial cells) in terms of their proliferation, migration and signaling aspects?
  • Demonstrate an independent action of EPO on HRECs by deactivating the  EPO-R and/or VEGFR or by non-receptor mediated action on PI-3 kinase/PKC/AKT signals?

Human Vitreous, Plasma and Cadaver eye samples were collected from the Regional Institute of Government Ophthalmic Hospital, Chennai. Invitro Culturing of Human Retinal Endothelial Cells (Primary Cell Culture), ELISA, immunohistochemistry, western blot analysis and migration assay have revealed that EPO protects the retinal ganglion cells and photoreceptors. However; EPO ineffective in providing protection in diabetic retinopathy and the effect of EPO signaling in HRECs remains still unknown.  Another aspect with therapeutic potential yet to be understood is if EPO uses the same angiogeneic pathways as VEGF or if it acts independent of VEGF

4. MDRF Rural Tele-ophthalmology Project- supported by World Diabetes Foundation (WDF), Denmark
Dr. M. Rema, Dr. V. Prathiba, Dr. R. Rajalakshmi and Dr. R. Guha Pradeepa

This project aims to screen for eye related disorders in diabetic subjects in rural areas using telemedicine as a novel tool. It further aims to encourage community participation by empowering the local people especially women and youth to become educators and spokespersons to adopt a healthy lifestyle and thereby play a significant role in preventing diabetes related eye disorders in the family and in the community at large.

Tele-Ophthalmology can help reach the right treatment at the right time to rural patients, which is otherwise difficult in remote areas, given that there is a huge mismatch of resources, with over 95% medical facilities currently only available to 20% of the urban population of India. This facility can be made use of effectively leading to cost effectiveness and increased total quality working hours.

 
 
Portfolio of Past Activities of the Department
 
 
  • Clinic based studies: The prevalence of diabetic retinopathy[DR] both in type 1 and type 2 diabetes, its prevalence at diagnosis of diabetes, vascular complications in MODY with special reference to retinopathy and familial clustering were studied. Visual outcomes at one-year follow-up after pan-retinal photocoagulation in type 2 diabetic subjects with proliferative diabetic retinopathy (PDR) and associated risk factors were also studied. The status of DR following cataract extraction in Type 2 diabetes mellitus patients was assessed in a retrospective analysis of data from records of Type 2 diabetic patients who underwent cataract extraction between 1996 -2001[223 eyes]. Progression of retinopathy was observed in 44% of the eyes after cataract surgery and visual acuity improved in 40% of eyes that underwent laser therapy after cataract extraction.
  • Population-based studies: These included the Chennai Urban Population Study (CUPS) and Chennai Urban Rural Epidemiology Study (CURES)] on the burden of eye diseases in diabetes with particular reference to DR, cataract, glaucoma etc,.

    The CURES Eye study conducted in Type 2 diabetic individuals showed that 17.6% had DR in Chennai i.e. one in 5 diabetic subjects have DR. The prevalence of DR was lower than in western population or other Asian populations.

    CURES also identified that gender (males being at higher risk), duration of diabetes, HbA1c , serum triglyceride and macroalbuminuria were risk factors for DR.  The relationship between DR and other microvascular complications and coronary artery disease in urban Type 2 diabetic subjects were also studied. The CURES study revealed that there was a significant association of serum triglycerides with DR and LDL cholesterol with diabetic macular edema [DME] and this association was present even after adjusting for confounding factors.
  • Biochemical Studies: The role of growth factors, adhesion molecules and other secondary messengers in the pathogenesis of diabetes and its progression to diabetic retinopathy was studied. Studies related to antioxidants and reactive oxygen species, Advanced Glycation Endproducts (AGEs) and its association with diabetic microangiopathy were conducted. The association of advanced glycation index (AGI), a simple assay to detect AGEs in serum, with severity of DR in type 2 diabetic subjects was studied and the results revealed that AGI showed a significant association with the severity of DR and, could hence be used as a prognostic tool to predict the development and progression of DR.
  • Genetic Studies: Research on the genetics of diabetic eye complications with particular reference to DR has identified that there is a strong familial and genetic predisposition for the development of DR were also carried out. Three important promoter polymorphisms in the RAGE gene were screened for, namely; the –374T/A, -429 T/C and 63 base pair deletion, which have shown to increase RAGE expression. We have found moderate association with –374 T/A polymorphism with non-proliferative diabetic retinopathy[NPDR] subjects. Additionally we have also screened for novel variants in the PEDF gene and studied the association on selected SNPs with diabetic retinopathy. A novel polymorphism was found which is located at the intron 1 region of the PEDF gene.  The Met 72Thr variant turned out to be a significant SNP for NPDR and PDR subjects, suggesting that PEDF variants are equally important in determining the risk of DR. A case control study carried out to screen five important functional polymorphism in the VEGF gene, in diabetic subjects with DR and without DR revealed that with respect to the DME group, significant associations were observed at the genotype level of – 2578 AA genotype and -634 polymorphisms with NPDR group carrying the CG heterozygous genotype when compared to the DM control group.  
  • Cell and Molecular Biology: Studies were carried out to investigate the effect curcumin induced on proliferation of Human Retinal Endothelial Cells (HREC) and to elucidate the possible mechanisms of anti-angiogenic activity of curcumin (deferuloylmethane). The results showed that curcumin effectively inhibited endothelial cell proliferation in a dose dependent manner. Curcumin also showed a significant reduction of intracellular ROS generation in HRECs. Additionally, VEGF mediated membrane associated changes in the PKC b II translocation in HREC was inhibited by 31% on treatment with 10mM curcumin. These data suggest an underlying mechanism whereby curcumin induces the apoptosis in HRECs by the regulation of intracellular ROS generation, VEGF expression and release, and VEGF-mediated PKC-betaII translocation. Another study elicited the inhibitory effect of curcumin on SDF-1alpha-induced HREC migration. The plausible mechanism of action could be upstream blockage of Ca(2+) influx and the downstream reduction of PI3-K/AKT signals
 
  Future trends  
 
  • To provide training in primary endothelial cell culture and epidemiological assessment of retinal problems.

 
  Facilities     
 


An array of sophisticated equipments is available at the department

  • Diagnosing eye disorders related to diabetes.
  • Indirect ophthalmoscopes with accessories
  • Slit lamp biomicroscopy
  •  FF450 PLUS Fundus digital camera 
  • Optical coherence Tomography (OCT)
  • Computerized field testing for glaucoma. 
  • Therapeutic facilities include state-of-the-art equipment
  • Argon laser treatment  &
  • ND-Yag laser for treatment of diabetic retinal disorders
  • Phacoemulsification equipment for cataract surgery                               
  • Central grading centre for diabetic retinopathy as per international standards-– the Early Treatment Diabetic Retinopathy Study (ETDRS) system.
  • Primary retinal endothelial cell culture facility has been established to investigate the effect of curcumin on the proliferation of Human Retinal Endothelial Cells (HREC) under in vitro conditions and also to elucidate the possible mechanisms of its action on the mediators of angiogenesis.
 
     
       
       
     
     
     
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