Abstract
or laser photocoagulation therapies used to treat retinal neovascularisation are either not effective in all patients or inherently
destructive to the retina. Therefore, new therapeutic targets are
urgently required. In the present study, we have investigated the
contribution of TRPV1 and TRPV4 channels to retinal angiogenesis in vitro and ischemia-driven retinal neovascularisation in vivo.
TRPV1 and TRPV4 mRNA and protein expression were identified
in primary bovine retinal endothelial cells (RMECs) using RT-PCR
and western blot analysis. Strong immunolabelling for these channels was also detected in RMECs and their functional expression
confirmed by whole-cell patch-clamp recording. Pharmacological
inhibition of TRPV1 and TRPV4 channels suppressed in vitro retinal angiogenesis through a mechanism specifically involving the
modulation of tubulogenesis. TRPV1 and TRPV4 channel blockade
had no effect on VEGF-induced angiogenesis in vitro. Inhibition of
either channel reduced retinal neovascularisation and promoted
reparative angiogenesis in the oxygen-induced mouse model of
ischemic retinopathy. Using proximity ligation assays and patchclamp recording, we observed that TRPV1 and TRPV4 form functional heteromeric channel complexes in RMECs in vitro. We conclude
that retinal endothelial TRPV1 and TRPV4 channels may provide
new targets for therapeutic intervention in ischemia-induced vasoproliferative diseases of the retina.
| Original language | English |
|---|---|
| Pages | 150 |
| Number of pages | 1 |
| Publication status | Published - 2018 |
| Event | XXIII Biennial Meeting of the International Society for Eye Research - Belfast, United Kingdom Duration: 09 Sep 2018 → 13 Sep 2018 |
Conference
| Conference | XXIII Biennial Meeting of the International Society for Eye Research |
|---|---|
| Country | United Kingdom |
| City | Belfast |
| Period | 09/09/2018 → 13/09/2018 |
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Involvement of TRPV1 and TRPV4 Channels in Pathological Retinal Angiogenesis : Oral presentation. / Curtis, Timothy; O'leary, Catriona; McGahon, Mary; Ashraf, Sadaf; McNaughten, Jennifer; Fernandez, Jose; Stitt, Alan; McGeown, Graham.
2018. 150 XXIII Biennial Meeting of the International Society for Eye Research, Belfast, United Kingdom.Research output: Contribution to conference › Other
TY - CONF
T1 - Involvement of TRPV1 and TRPV4 Channels in Pathological Retinal Angiogenesis
T2 - Oral presentation
AU - Curtis, Timothy
AU - O'leary, Catriona
AU - McGahon, Mary
AU - Ashraf, Sadaf
AU - McNaughten, Jennifer
AU - Fernandez, Jose
AU - Stitt, Alan
AU - McGeown, Graham
PY - 2018
Y1 - 2018
N2 - Visual loss in retinal ischemic diseases, such as retinopathy of prematurity and diabetic retinopathy, is closely associated with the development of pathological retinal angiogenesis. Current anti-VEGFor laser photocoagulation therapies used to treat retinal neovascularisation are either not effective in all patients or inherentlydestructive to the retina. Therefore, new therapeutic targets areurgently required. In the present study, we have investigated thecontribution of TRPV1 and TRPV4 channels to retinal angiogenesis in vitro and ischemia-driven retinal neovascularisation in vivo.TRPV1 and TRPV4 mRNA and protein expression were identifiedin primary bovine retinal endothelial cells (RMECs) using RT-PCRand western blot analysis. Strong immunolabelling for these channels was also detected in RMECs and their functional expressionconfirmed by whole-cell patch-clamp recording. Pharmacologicalinhibition of TRPV1 and TRPV4 channels suppressed in vitro retinal angiogenesis through a mechanism specifically involving themodulation of tubulogenesis. TRPV1 and TRPV4 channel blockadehad no effect on VEGF-induced angiogenesis in vitro. Inhibition ofeither channel reduced retinal neovascularisation and promotedreparative angiogenesis in the oxygen-induced mouse model ofischemic retinopathy. Using proximity ligation assays and patchclamp recording, we observed that TRPV1 and TRPV4 form functional heteromeric channel complexes in RMECs in vitro. We concludethat retinal endothelial TRPV1 and TRPV4 channels may providenew targets for therapeutic intervention in ischemia-induced vasoproliferative diseases of the retina.
AB - Visual loss in retinal ischemic diseases, such as retinopathy of prematurity and diabetic retinopathy, is closely associated with the development of pathological retinal angiogenesis. Current anti-VEGFor laser photocoagulation therapies used to treat retinal neovascularisation are either not effective in all patients or inherentlydestructive to the retina. Therefore, new therapeutic targets areurgently required. In the present study, we have investigated thecontribution of TRPV1 and TRPV4 channels to retinal angiogenesis in vitro and ischemia-driven retinal neovascularisation in vivo.TRPV1 and TRPV4 mRNA and protein expression were identifiedin primary bovine retinal endothelial cells (RMECs) using RT-PCRand western blot analysis. Strong immunolabelling for these channels was also detected in RMECs and their functional expressionconfirmed by whole-cell patch-clamp recording. Pharmacologicalinhibition of TRPV1 and TRPV4 channels suppressed in vitro retinal angiogenesis through a mechanism specifically involving themodulation of tubulogenesis. TRPV1 and TRPV4 channel blockadehad no effect on VEGF-induced angiogenesis in vitro. Inhibition ofeither channel reduced retinal neovascularisation and promotedreparative angiogenesis in the oxygen-induced mouse model ofischemic retinopathy. Using proximity ligation assays and patchclamp recording, we observed that TRPV1 and TRPV4 form functional heteromeric channel complexes in RMECs in vitro. We concludethat retinal endothelial TRPV1 and TRPV4 channels may providenew targets for therapeutic intervention in ischemia-induced vasoproliferative diseases of the retina.
M3 - Other
SP - 150
ER -