Purpose: Recent evidence shows that much of the protein in the anterior chamber aqueous humor enters diffusively through the root of the iris. The proximity of the protein entry point to the trabecular meshwork suggests that the protein content of the aqueous humor in the trabecular meshwork might be much higher than previously suggested. The authors were interested in investigating the possible hydrodynamic implications of these proteins.
Methods: Bovine eyes were perfused with concentrations of bovine serum in buffer ranging from 0% to 15% to determine the effect on outflow resistance. Immunohistochemical methods were used on these eyes and unperfused eyes to determine the distribution of albumin in the anterior segment.
Results: Preliminary perfusion studies suggested that increasing the concentration of serum in buffer from 0% to 15% decreased the rate of "wash-out" in bovine eyes, with a 15% solution essentially eliminating the wash-out phenomenon. Perfusion of a series of bovine eyes with a total of 5 ml of 15% serum in buffer showed a "wash-out" rate of 0.0498 +/- 0.0428 ([microliters/min/mm Hg]/[ml perfusate]), whereas control eyes perfused with buffer washed-out at a rate of 0.1677 +/- 0.0271 (P < 0.05); a second series of eyes perfused with a total of 10 ml of 15% serum washed-out at a rate of 0.0533 +/- 0.0294, whereas control eyes had a rate of 0.1813 +/- 0.0342 (P < 0.02). Immunohistochemical investigations showed significant quantities of albumin in the outflow pathway of unperfused eyes, whereas perfusion with buffer eliminated this protein; perfusion with 10% to 15% serum in buffer maintained the level of albumin in the outflow pathway similar to that found in unperfused eyes. Use of cuprolinic blue in a critical electrolyte concentration confirmed previous findings that sulfated proteoglycans are not eliminated from the trabecular meshwork during wash-out.
Conclusions: Wash-out in nonhuman species may result from progressive depletion of an anterior segment depot of plasma-derived proteins entering the trabecular meshwork. Modeling studies confirm that plasma-derived proteins in the aqueous humor of the trabecular meshwork can generate a significant fraction of aqueous outflow resistance. The lack of wash-out in human eyes suggests that this system may maintain flow resistance in a fashion fundamentally different from other species.