Eyeworld

FEB 2012

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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24 EW NEWS & OPINION Could continued from page 23 cataract compared to the non-Indian population.10,11 This suggests that be- sides environmental and nutritional factors, there may be genetic factors predisposing Indians to cataract as well. In addition to decreased dietary intake, low plasma levels of vitamin C in the Indian population may re- flect a genetic difference in the hap- toglobin Hp allele status (Hp1 vs. Hp2). In India the Hp2-2 phenotype is much more common compared to Europeans (70-80% compared to 30- 40% of the population). Conversely, the Hp1-1 phenotype is much less common compared to Europeans (<3% in India compared to 15-20% in Europe).12 Other studies have re- ported a 20% reduction in plasma vitamin C levels in patients with the Hp2-2 phenotype compared to those with Hp1-1.13 A study from Toronto found vitamin C deficiency in 17% of subjects with Hp2-2 compared to 11% with either Hp1-1 or 2-1.14 An important function of hap- toglobin is to bind hemoglobin pre- venting peroxidation by free iron. However the Hp2-2 phenotype dis- plays low hemoglobin affinity, and the levels of free plasma hemoglobin are therefore higher leading to higher oxidant stress. Lower vitamin C plasma levels in haptoglobin deficient Hp2-2 individuals may be caused by the reduction of free iron.15 Therefore, genetic haptoglo- bin differences might also contribute to the lower plasma vitamin C levels reported for South Asians compared to those of European or African an- cestry in the U.K.16 or for Indians compared to Chinese in Singapore.17 Finally, the risk of vitamin C deficiency due to low dietary intake is affected by Hp genetic status (odds ratio=1.7 for Hp1-1 or 2-1, compared to 4.8 for Hp2-2).14 This suggests that the risk of vitamin C deficiency with the Hp2-2 phenotype is great- est when combined with lower dietary intake of vitamin C—a combination that may be a factor behind the increased prevalence of cataract among Indians. Dr. Chang: What follow-up studies are you planning to do? Dr. Ravindran: The very high proportion of the population with the Hp2-2 phenotype suggests a pos- sible genetic factor contributing to low vitamin C levels in Indians be- yond dietary deficiency alone. If we can confirm a correlation between cataract and low plasma vitamin C, the haptoglobin 2-2 phenotype, and decreased levels of haptoglobin and iron transport proteins, we can hy- pothesize a mechanism of cataract pathogenesis that is relevant to our population. For this reason we have initiated studies looking at the vita- min C levels in plasma, in aqueous, and in the lens, along with hapto- globin analysis and biomarkers of iron. This study is the next step in testing our hypothesis. Dr. Chang: What are the practi- cal implications of your study? Would there be a viable approach to providing vitamin C supplementa- tion to reduce the cataract burden in undernourished populations? Dr. Ravindran: We believe that dietary fortification with vitamin C could reduce the prevalence of cataract in our population in the long term. For this reason, we are also designing a long-term commu- nity-based vitamin C supplementa- tion study to evaluate this and other potential benefits. Several random- ized control trials with vitamin C reported no benefit in cataract pre- vention. However, these studies were done with western populations, where we believe that the majority would have had the haptoglobin 1-1 or 1-2 phenotype and reasonably good dietary intake. In such a set- ting, it is understandable why addi- tional vitamin C supplementation might not have been helpful. We hypothesize that the Indian popula- tion, with its lower dietary intake of vitamin C and higher genetic risk factors for lower plasma vitamin C levels, could benefit from additional supplementation. Our results highlight the poor nutritional status of many older peo- ple in India, especially those with low incomes. The very high preva- lence of cataract among the elderly (currently 6-7% of the population >age 60) will nearly double in the next 20 years, placing a heavy bur- den on India's healthcare system. Any method to slow down or post- pone the onset of cataract would therefore have a major impact and is a focus of our research. EW References 1. Taylor A, Jacques PF, Nowell T, et al. Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake. Curr Eye Res 1997;16:857–64. 2. Shui YB, Holekamp NM, Kramer BC, et al. The gel state of the vitreous and ascorbate- dependent oxygen consumption: relationship to the etiology of nuclear cataracts. Arch Ophthalmol 2009;127:475–82. 3. Shang F, Lu M, Dudek E, et al. Vitamin C and vitamin E restore the resistance of GSH-de- pleted lens cells to H2O2. Free Radic Biol Med 2003;34:521–30. 4. Consul BN, Mathur GB, Mehrotra AS. Aqueous humor ascorbic acid in normal, cataractous and aphakic Indian subjects. J All India Ophthalmol Soc 1968;16:105–8. 5. Dherani M, Murthy GV, Gupta SK, et al. Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population. Invest Ophthal- mol Vis Sci 2008;49:3328–35. 6. Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844– 51. 7. Krishnaiah S, Vilas K, Shamanna BR, et al. Smoking and its association with cataract: results of the Andhra Pradesh Eye Disease Study from India. Invest Ophthalmol Vis Sci 2005;46:58–65. 8. Nirmalan PK, Krishnadas R, Ramakrishnan R, et al. Lens opacities in a rural population of southern India: the Aravind Comprehensive Eye Study. Invest Ophthalmol Vis Sci 2003;44:4639–43. 9. Vashist P, Talwar B, Gogoi M, et al. Prevalence of cataract in an older population in India: the India Study of Age-related Eye Disease. Ophthalmology 2011;118:272–8. 10. Wong TY. Cataract extraction rates among Chinese, Malays and Indians in Singapore. Arch Ophthalmol 2001; 119:727-732. continued on page 26 February 2012

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