Impact of age, systemic glucocorticoids, and progressive knee arthritis on specific mRNA levels in different areas of the rabbit cornea.
OBJECTIVE
To determine the influence of factors such as age, osteoarthritis (OA), and glucocorticoid treatment on total RNA and mRNA regulation in the cornea and how these factors differ between prepupillary and peripheral areas of the cornea.


METHODS
Molecular analyses of corneal tissue were performed using rabbits of different age groups and skeletally mature animals that had undergone anterior cruciate ligament (ACL) transection, an established model of knee OA. Systemic glucocorticoids were administered to cohorts of the osteoarthritic and control animals to determine the influence of distal joint disease on the corneal response. Corneal tissue was analyzed for changes in mRNA levels for several relevant genes: collagen I, collagen III, collagen V, decorin core protein, cyclooxygenase-2 (COX-2), glucocorticoid receptor, and the housekeeping gene beta-actin.


RESULTS
The corneal tissue was found to have diminishing total RNA with age, which is consistent with previous studies in the literature. Interestingly, in skeletally mature animals, distal joint OA was found to affect corneal mRNA levels for several important structural and inflammatory genes (collagen I, decorin core protein, and COX-2) in a manner that progressed with OA progression. Although systemic glucocorticoid treatment did not alter mRNA levels in the normal cornea, it did counteract the changes observed early after OA induction (3 weeks) while having less of an effect in later, more established arthritis (6 weeks).


CONCLUSIONS
This study reveals that distal joint OA can affect mRNA levels for several structural and inflammatory genes of the cornea, changes that seem to be suppressed by systemic glucocorticoid treatment. These findings indicate that OA has associated systemic factors that influence corneal cell metabolism.
Kydd
Alison S
AS
McCaig Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Reno
Carol R
CR
Tsao
Helen W
HW
Hart
David A
DA
D000199:Actins / Q000235:genetics; D000375:Aging / Q000502:physiology*; D000818:Animals; D003315:Cornea / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D024022:Fibrillar Collagens / Q000235:genetics; D005938:Glucocorticoids / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000235:genetics
D000199:Actins; D058575:Decorin; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D005938:Glucocorticoids; D011509:Proteoglycans; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000077555:Methylprednisolone Acetate; D051546:Cyclooxygenase 2; D008775:Methylprednisolone