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The iCre-DTA176 Mouse Exhibits Canonical Spontaneous Network Activity Associated With Retinal Degeneration
Samuel William Fifield-Smith1, Lay Khoon Too2, Thomas Francis Cahir1
1Neuroscience Theme, School of Medical Sciences, The University of Sydney, Sydney, Australia.
Investigative Ophthalmology & Visual Science
|June 15, 2026
Summary
Spontaneous rhythmic activity in degenerating retinas, driven by gap junctions, was studied in a novel mouse model. Suppressing these oscillations improved vision restoration signals.
Area of Science:
- Neuroscience
- Ophthalmology
- Retinal Degeneration Research
Background:
- Spontaneous rhythmic activity is common in degenerating retinas.
- This activity hinders vision restoration efforts.
- Understanding these oscillations is crucial for developing effective therapies.
Purpose of the Study:
- To investigate spontaneous network activity in the Rho-iCre-DTA176 mouse model of retinal degeneration.
- To identify the mechanisms underlying this aberrant activity.
- To assess the functional consequences of this activity on vision restoration.
Main Methods:
- Extracellular recordings from isolated retinas using multielectrode arrays.
- Characterization of spontaneous and optogenetically evoked retinal ganglion cell (RGC) activity.
- Pharmacological disruption of electrical coupling with meclofenamic acid (MFA).
Main Results:
- Rho-iCre-DTA176 retinas showed pronounced oscillatory burst firing in RGCs.
- MFA abolished rhythmic bursting, indicating a gap-junction-dependent network origin.
- Suppression of oscillations improved the signal-to-noise ratio of evoked responses.
Conclusions:
- Pathological retinal oscillations in this model are gap-junction-dependent.
- These oscillations mimic those in other retinal degeneration models.
- The Rho-iCre-DTA176 mouse is a valid model for testing vision restoration strategies.

