Purpose: The etiology of glaucoma is still unknown, though several mechanisms have been proposed to contribute to the changes of the optic nerve head (ONH). The most important known risk factor is increased intraocular pressure (IOP) and consequently, therapies available today focus on lowering IOP. However, there is also evidence that reduced ocular perfusion pressure (OPP) and altered blood flow regulation may play a role in the development and progression of this disease. In the present study, we tested the hypothesis that ONH blood flow is autoregulated during isometric exercise induced changes in mean arterial blood pressure (MAP) and during suction cup induced changes in IOP. We also explored whether blood flow only depends on OPP, or also on absolute values of MAP and IOP. Additionally, we investigated the role of endothelin-1 (ET-1) on ONH blood flow regulation during isometric exercise.
Material and Methods: The present studies were performed in a total of 55 healthy young male and female subjects. The effect of MAP and IOP elevation on ONH blood flow as well as the combined increase in these 2 parameters were investigated in 40 volunteers. IOP was increased in stepwise increments using a suction cup with a force of 25 mmHg to 100 mmHg and MAP was elevated by means of isometric exercise. Fifteen subjects participated in the randomized, placebo-controlled cross-over trial investigating the effect of the selective endothelinA (ETA) receptor antagonist BQ-123 on ONH blood flow regulation during a six minutes squatting period. ONH blood flow was measured using laser Doppler flowmetry. OPP was calculated as 2/3*MAP-IOP.
Results: In the experiments investigating the combined increase in MAP and IOP, a highly significant correlation was found between ONH blood flow and IOP (p < 0.001) when data were grouped according to MAP values.
The correlation between ONH blood flow and MAP was much less pronounced when data were grouped according to IOP levels (p < 0.05). During all squatting periods OPP as well as ONH blood flow increased (p < 0.001 each). The increase in ONH blood flow was, however, less pronounced than the increase in OPP indicating for some degree of blood flow regulation.
BQ-123 did not change OPP or ONH blood flow at baseline. The response of OPP during isometric exercise was not altered by the ETA receptor antagonist. However, the increase in blood flow during squatting was more pronounced during BQ-123 than during placebo (p < 0.01).
Conclusion: Our results confirm that the ONH shows autoregulatory behavior during both an increase in OPP and a decrease in OPP.
Additionally, our data show that ONH blood flow is better regulated during changes in MAP than during an increase in IOP. Furthermore, ET-1 seems to play a role in the autoregulatory process of ONH blood flow during isometric exercise. These data indicate that the ET system is a potential target for eye diseases with abnormal autoregulation.