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Age-Dependent Control of Lens Growth by Hypoxia

¹From the Departments of Ophthalmology and Visual Sciences and ²Cell Biology and Physiology, Washington University, St. Louis, Missouri.

PURPOSE. The lens grows continuously throughout life, but the factors that influence the size of the adult lens are not known. Lens thickness is a significant risk factor for age-related cataract. It has been postulated that the hypoxic environment in the eye protects the lens from nuclear cataracts. The authors sought to determine whether the PO₂ in the eye regulates lens growth.

METHODS. Lens cell proliferation was determined by counting BrdU-labeled and total nuclei in the germinative zone in flatmounts of lens epithelia. Oxygen levels in the eye were altered by having rats breathe 11%, 21% (room air), or 60% oxygen. Oxygen levels in the vitreous were measured with a fiberoptic oxygen sensor.

RESULTS. The BrdU-labeling index in the germinative zone declined from approximately 3.5% at 1 month to less than 0.7% at 8 months. Raising oxygen levels in the eyes of 1-month-old animals did not alter the rate of lens cell proliferation. Elevating intraocular oxygen in animals older than 1 month increased proliferation to the more rapid rate seen at 1 month. Decreasing oxygen levels below their normally low level did not affect the BrdU-labeling index at any age. Chronic exposure to increased oxygen led to the production of more lens fiber cells and larger lenses.

CONCLUSIONS. Normal age-related decline in lens growth requires the low oxygen level normally present in the eye. Increases in lens cell number and mass may account for some of the increase in cataract risk caused by chronic exposure of the lens to elevated oxygen levels.