A brief photochemically induced oxidative insult causes irreversible lens damage and cataract. II. Mechanism of action.
Using photochemically induced oxidative stress and rat lenses in organ culture with 4% O2 and 4 microM riboflavin, it has been found that the observed changes in lens parameters are, in most cases, irreversible. This has made possible the elucidation of the sequence of biological changes leading to cataract. The earliest detectable changes in lens cell biology are observed in the epithelial cell redox set point and at the DNA level in terms of DNA integrity and 3H-thymidine incorporation followed by decreased membrane transport and changes in gene expression. Significant modification in classical cataract parameters such as hydration, steady state non-protein thiol, glyceraldehyde-phosphate-dehydrogenase activity and transparency occur at later times. The data suggest a definitive pattern of lens breakdown resulting in opacity starting at the epithelial cell level and leading to subsequent fibre cell involvement.
Spector
A
A
Department of Ophthalmology, College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA.
Wang
G M
GM
Wang
R R
RR
Li
W C
WC
Kleiman
N J
NJ
D000818:Animals; D015152:Blotting, Northern; D002386:Cataract / Q000209:etiology* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005821:Genetic Techniques; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008027:Light / Q000009:adverse effects*; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012256:Riboflavin / Q000009:adverse effects*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D013438:Sulfhydryl Compounds; D004247:DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012256:Riboflavin; D013936:Thymidine