Is hyperleptinemia involved in the development of age-related lens opacities?

Metabolic Research Laboratory
Clínica Universitaria de Navarra
University of Navarra
Edificio CIFA
Irunlarrea 1
31008 Pamplona
Spain
E-mail: jagomez{at}unav.es

Javier Salvador

Department of Endocrinology
Clínica Universitaria de Navarra
University of Navarra
31008 Pamplona
Spain

Gema Frühbeck

Department of Endocrinology & Metabolic Research Laboratory
Clínica Universitaria de Navarra
University of Navarra
31008 Pamplona
Spain

Dear Sir:

We read with great interest the recent article by Jacques et al (1) in which the relation between body mass index (BMI) and the development of age-related lens opacities in women is reported. In an elegant cross-sectional study, the authors indicate that BMI may be a risk factor for posterior subcapsular opacities. We approach this finding from a complementary point of view, by suggesting the involvement of leptin in the molecular mechanisms underlying cataract development.

Leptin is a 16-kDa pleiotropic cytokine expressed and secreted mainly by adipocytes, and it has a wide range of central and peripheral actions, including effects on body-weight homeostasis, reproduction, the immune system, angiogenesis, and blood pressure regulation. Plasma leptin concentrations are correlated with BMI and even more strongly with body fat content. Consequently, leptin concentrations are dramatically elevated in obese subjects, who exhibit hyperleptinemia and leptin resistance (2). Leptin has been shown to induce oxidative stress in both animals and humans. In fact, leptin increases the accumulation of reactive oxygen species in various cellular models (3, 4). Oxidative stress is an initiating factor for the development of maturity-onset cataracts, and increases in reactive oxygen species in the lens have been shown to be strongly involved in lens opacification leading to the formation of cataracts (5). In addition, BMI is highly associated with systemic oxidative stress as determined from creatinine-indexed urinary concentrations of 8-epi-prostaglandin F₂ (6). This finding reinforces the notion of a link between obesity, hyperleptinemia, and increased oxidative stress.

The deleterious effects of hyperleptinemia might also be involved in the development of other age-related eye diseases such as age-related maculopathy, because this degenerative condition of the retina and choroid is positively associated with BMI (7). Furthermore, high blood concentrations of leptin seem to be involved in the development of hypertensive and diabetic retinopathy as well as in retinal detachment (8–10), which shows that obesity-related hyperleptinemia may intervene in other eye diseases. It is our belief that studying the potential participation of leptin in the development of age-related cataracts and other eye diseases may provide valuable information concerning the etiology of these pathologies.

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. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292–5.
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. Spector A. Oxidative stress-induced cataract: mechanism of action. FASEB J 1995;9:1173–82.
6. Keaney JF Jr, Larson MG, Vasan RS, et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003;23:434–9.
7. Schaumberg DA, Christen WG, Hankinson SE, Glynn RJ. Body mass index and the incidence of visually significant age-related maculopathy in men. Arch Ophthalmol 2001;119:1259–65.
8. Uckaya G, Ozata M, Sonmez A, et al. Is leptin associated with hypertensive retinopathy? J Clin Endocrinol Metab 2000;85:683–7.
9. Uckaya G, Ozata M, Bayraktar Z, Erten V, Bingol N, Ozdemir IC. Is leptin associated with diabetic retinopathy? Diabetes Care 2000;23:371–6.
10. Gariano RF, Nath AK, D'Amico DJ, Lee T, Sierra Honigmann MR. Elevation of vitreous leptin in diabetic retinopathy and retinal detachment. Invest Ophthalmol Vis Sci 2000;41:3576–81.