Introduction. Elevated intraocular pressure (IOP) is
involved in the pathogenesis of almost all forms of glaucoma. Our hypothesis is that the human
trabecular meshwork (HTM) possesses homeostatic mechanisms to potentially
regulate IOP. In this study, we measured the effects of short and long time
exposures of high IOP insults on aqueous humor outflow facility (C=flow/pressure).
Methods. The
anterior segments of pairs of normal human eyes from post-mortem donors were
placed in organ culture and perfused for 24 h at constant flow of 3 ml/min (Johnson&Tschumper, EER 49, 113,
1989). After reaching baseline
values, the flow of one eye was raised to obtain a continuous pressure of 60 to
70 mm Hg for a period of 7 days (n=9).
The flow of the fellow eye
was maintained at 3 ml/min
serving as a control (n=8).
Selected eyes fulfilled the inclusion criteria of C0 values between 0.06 and 0.4, intact RNA recovery and good light
microscopy morphology. Percent
change of facility from the baseline (C/C0) was computed at 6 h, 24 h, 48 h, 4
days and 7 days. Results. Average facility at baseline was 0.13 ± 0.02 (n=17). After 6 h, the
percent change of C (C/C0) of the treated eye was 11.0 ± 4.6% versus that of 3.7 ± 3.8% in the control eyes (p= 0.26). At 24 h, the facility of the high IOP eyes had increased
26.1 ± 6.0% compared to
10.9 ± 4.1% in the
controls (p= 0.06).The difference between treated and untreated eyes continued
to increase and became significant at 4 days, with values of 32.9 ± 8.4% and 7.4 ± 7.6% respectively
(p=0.04). At 7 days, no
significant effect was apparent (8.9 ± 7.9% versus 1.1 ± 12.7% in controls
(p= 0.6). Conclusions
This study provides some evidence that outflow facility may be regulated,
but with a longer latency time than perhaps previously appreciated. After 1-4
days of elevated IOP, outflow facility increases. Understanding the potential
regulatory mechanisms involved in this observation might have important
implications for glaucoma. CR:
None. Support: NIH grant EY11906
and EY1894, the Glaucoma Research Foundation, NEI core grant P30EY05722 and
Research to Prevent Blindness. TB
is a Jules and Doris Stein RPB Professor Awardee.