Long-Term Effects on Retinal Structure and Function in a Mouse Endothelin-1 Model of Retinal Ganglion Cell...

Area of Science:

• Ophthalmology
• Retinal Diseases
• Vascular Biology

Background:

• Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in various vascular pathologies.
• Understanding ET-1's role in retinal damage is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the long-term consequences of ET-1-induced retinal pathologies in a mouse model.
• To utilize clinically relevant tools for assessing retinal changes.

Main Methods:

• Adult mice received intravitreal injections of varying doses of ET-1 or a control (PBS).
• Retinal function was assessed using electroretinogram (ERG) and optical coherence tomography (OCT), including Doppler OCT.
• Retinal nerve fiber layer (RNFL) thickness and retinal ganglion cell (RGC) survival were quantified at multiple time points post-injection.

Main Results:

• ET-1 induced immediate retinal arterial constriction and transiently reduced blood flow and ERG responses.
• A significant reduction in RNFL thickness was observed in all ET-1 groups by day 56, with earlier onset in the highest dose group.
• Dose-dependent RGC loss was evident by day 28, with significant loss observed in central and midperipheral retina by day 56 in lower-dose groups.

Conclusions:

• ET-1 injection leads to transient retinal vascular constriction and functional impairment.
• A dose-dependent, gradual loss of RNFL and RGCs occurs following ET-1 administration.
• These findings highlight ET-1's significant impact on retinal structure and function, relevant to clinical conditions.