Reply to J Gómez-Ambrosi et al

Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University
Laboratory for Nutrition and Vision Research
711 Washington Street
Boston, MA 02115
E-mail: ataylor{at}hnrc.tufts.edu

Dear Sir:

Gómez-Ambrosi et al posit an attractive hypothesis: that the relation we reported between overweight and elevated odds for posterior subcapsular opacities (1) may have etiologic factors that include responses to elevated leptin. Their hypothesis is based on observations that 1) overweight is associated with elevated leptin concentrations, 2) elevated leptin concentrations appear to cause at least transient elevations in reactive oxygen species (2), and 3) elevated reactive oxygen species have been related to cataractogenesis. To date, there is a paucity of information that would allow direct investigation of this hypothesis.

What is known is that reactive oxygen species are second messengers resulting from leptin-induced, leptin receptor-mediated signaling in endothelial cells, and chronic oxidative stress in endothelial cells under hyperleptinemia may activate atherogenic processes and contribute to the development of vascular pathology (3). Consistent with these data, leptin was found to be an angiogenic factor, and its vitreous concentrations are associated with angiogenic eye diseases such as proliferative diabetic retinopathy. In addition to involving oxidants, the biological effects of leptin appear to involve antioxidants and several growth factors, including vascular endothelial growth factor and pigment epithelium-derived factor, which are also present in the vitreous of eyes with angiogenic diseases (4). However, although a leptin receptor was found in the choroid, sclera, and connective tissues of the limbus, there is no evidence as yet for a leptin receptor in the lens (5). If this lack of evidence were supported by further research, it would imply that the roles of leptin in the etiology of cataract development are probably indirect and perhaps reflect generalized oxidative stress that originates in non-lens tissues and is comparable to the oxidative stress induced by smoking (6). This would make elucidation of the roles of leptin more difficult than if a direct role of leptin in lens cell function could be posited.

REFERENCES

1. Jacques PF, Moeller SM, Hankinson SE, et al. Weight status, abdominal adiposity, diabetes, and early age-related lens opacities. Am J Clin Nutr 2003;78:400–5.
2. Savini I, Catani MV, Rossi A, et al. Vitamin C recycling is enhanced in the adaptive response to leptin-induced oxidative stress in keratinocytes. J Invest Dermatol 2003;121:786–93.
3. Bouloumie A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J 1999;13:1231–8.
4. Yamagishi S, Amano S, Inagaki Y, Okamoto T, Takeuchi M, Inoue H. Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res 2003;65:186–90.
5. Camand O, Turban S, Abitbol M, Guerre-Millo M. Embryonic expression of the leptin receptor gene in mesoderm-derived tissues. C R Biol 2002;325:77–87.
6. West SK. Smoking and the risk of eye disease. In: Taylor A, ed. Nutritional and environmental influences on the eye. Boca Raton, FL: CRC Press, 1999:151–64.