More than 90% of ocular diseases, such as glaucoma, age-related macular degeneration, and dry eye, are age-related with the incidence increasing with age. Furthermore, although retinitis pigmentosa and myopia may be associated with hereditary factors, they are also considered age-related diseases since they progress with aging. Thus, instead of targeting individual diseases, a new approach aimed at targeting aging itself is being examined.
The most established current anti-aging approach is calorie restriction, considered to induce various gene expressions such as anti-oxidative enzymes contributing to life extension. At first, we confirmed that conditions under increased oxidative stresses, including genetically modified animals, such as Sod-1 knockout mice (KO), Mev1 transgenic mice, and Nrf-2 KO mice, and smoking induces a decrease in tear secretion resulting in dry eye. Recently, we found that dietary supplements containing lactoferrin or lactic acid bacteria suppress oxidative stress in the lacrimal glands, these results need to be considered in association with the current advances in the microbiome research. It is now possible to promote the clinical use of those supplements to increase tear secretion. Calorie restriction (CR) activates longevity gene sirtuins. We also have shown that agents activating sirtuins, such as resveratrol or nicotinamide mononucleotide (NMN) have retinal protective effects. Particularly, NMN is promising since we have confirmed its therapeutic effect against retinitis pigmentosa. Ketone bodies are considered another mechanistic target of CR. We developed eye drops containing ketone bodies, and confirmed a therapeutic effect similar to that of CR. Now we are expanding our investigations to include new therapies for dry eye and neuroprotection for the retina and the optic nerve. Other pathways such as endoplasmic reticulum (ER) stress, inhibition of hypoxia-inducible factor (HIF), and inhibition of the insulin-like growth factor (IGF) are also considered to be targets for the anti-aging approach.
Taken together, the new strategy "anti-aging" is one approach in dealing with ocular diseases. The anti-aging approach is promising as the next generation of preventive medicine focusing on aging for the current era with increased health care expenditures.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 121:232-248, 2017.