Alterations in retinal perfusion contribute to numerous sight-threatening disorders, including diabetic retinopathy, glaucoma and retinal branch vein occlusions. Understanding the molecular mechanisms involved in the control of blood flow through the retina and how these are altered during ocular disease could lead to the identification of new targets for the treatment of these conditions. Retinal arterioles are the main resistance vessels of the retina, and consequently, play a key role in regulating retinal hemodynamics through changes in luminal diameter. In recent years, we have made significant progress in understanding the generation of myogenic constriction in retinal arterioles. We have shown that Ca2+ sparks play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of arterial vessels. We have also found that L-type and T-type Ca2+ channel activity promotes myogenic constriction while BK and Kv channels oppose the generation of myogenic tone. Our studies have also indicated that ClCa channels contribute to agonist- but not pressure-induced tone development in retinal arterioles. To identify the primary mechanosensor involved in myogenic signalling in retinal arterioles, we studied the potential involvement of transient receptor potential (TRP) channels. These studies revealed that retinal vascular smooth muscle cells express a range of mechanosensitive TRP channels, but that only TRPV2 appears to contribute to myogenic signalling in this vascular bed. Our findings provide new insights into the molecular mechanisms controlling myogenic constriction in the retina, and provide a basis for future studies aimed at better understanding the mechanisms responsible for the disruption of retinal perfusion in ocular disease.
|Publication status||Published - 13 Sep 2018|
|Event||International Society for Eye Reserach - Belfast, United Kingdom|
Duration: 10 Sep 2018 → 13 Sep 2018
|Conference||International Society for Eye Reserach|
|Abbreviated title||ISER 2018|
|Period||10/09/2018 → 13/09/2018|