Abstract
Purpose
This research elucidates the degeneration of retinal ganglion cells (RGCs) triggered by corneal alkali burns. The focus is on investigating whether the loss of RGCs can be ascribed to secondary cell death mechanisms mediated through retinal gap junctions (GJ) and on evaluating the potential of gap junction blockers as immediate neuroprotective interventions.
Methods
An experimental corneal alkali burn model was established in C57BL/6J and connexin36 knockout homo mice by administrating sodium hydroxide solution on the mice's cornea. The GJ blocker meclofenamic acid (MFA, 500µM) was delivered by intravitreal injection. The retinal ganglion cell loss was assessed by TUNEL staining, and single-cell recordings were performed to evaluate RGCs' morphological and functional changes.
Results
Our results demonstrated a time-dependent increase peaking at 24 hours in RGCs loss after the corneal alkali burn, which was characterized as expanding from the peripheral to the central part. The study revealed a notable reduction in the light sensitivity and the amplitudes of excitatory (EPSC) and inhibitory (IPSC) postsynaptic currents in ON alpha ganglion cells after 6 hours corneal alkali burn. Additionally, a decline in the amplitude of EPSC was observed in OFF alpha ganglion cells. Crucially, Cx36 KO homo mice exhibited a significantly increased survival of RGCs. We found that alkali-burnt eyes with MFA largely lessened light intensity reduction in ON alpha ganglion cells.
Conclusions
Our results indicated that Cx36 as gap junctions mediates the secondary cell death of RGCs after corneal alkali injuries, forming the possible target for neuroprotective treatment.
This research elucidates the degeneration of retinal ganglion cells (RGCs) triggered by corneal alkali burns. The focus is on investigating whether the loss of RGCs can be ascribed to secondary cell death mechanisms mediated through retinal gap junctions (GJ) and on evaluating the potential of gap junction blockers as immediate neuroprotective interventions.
Methods
An experimental corneal alkali burn model was established in C57BL/6J and connexin36 knockout homo mice by administrating sodium hydroxide solution on the mice's cornea. The GJ blocker meclofenamic acid (MFA, 500µM) was delivered by intravitreal injection. The retinal ganglion cell loss was assessed by TUNEL staining, and single-cell recordings were performed to evaluate RGCs' morphological and functional changes.
Results
Our results demonstrated a time-dependent increase peaking at 24 hours in RGCs loss after the corneal alkali burn, which was characterized as expanding from the peripheral to the central part. The study revealed a notable reduction in the light sensitivity and the amplitudes of excitatory (EPSC) and inhibitory (IPSC) postsynaptic currents in ON alpha ganglion cells after 6 hours corneal alkali burn. Additionally, a decline in the amplitude of EPSC was observed in OFF alpha ganglion cells. Crucially, Cx36 KO homo mice exhibited a significantly increased survival of RGCs. We found that alkali-burnt eyes with MFA largely lessened light intensity reduction in ON alpha ganglion cells.
Conclusions
Our results indicated that Cx36 as gap junctions mediates the secondary cell death of RGCs after corneal alkali injuries, forming the possible target for neuroprotective treatment.
| Original language | English |
|---|---|
| Title of host publication | Investigative Ophthalmology & Visual Science |
| Volume | 65 |
| Publication status | Published - 1 Jun 2024 |
| Event | The International Conference of Vision and Eye Research (iCover2024) - Hong Kong, Hong Kong, China Duration: 23 May 2024 → 24 May 2024 |
Conference
| Conference | The International Conference of Vision and Eye Research (iCover2024) |
|---|---|
| Abbreviated title | ARVO 2024 |
| Country/Territory | China |
| City | Hong Kong |
| Period | 23/05/24 → 24/05/24 |