Abstract
Purpose :
Pressurized airwaves may cause traumatic retinal injury (TRI), and moderate pressures at 3-5 psi are highly harmful to the human body, but it has been unclear how they mediate TRI and how we could rescue neurons from pressure-induced injury. Retinal neurons express mechanical sensitive ion channels (MSCs), and this study attempts to determine the MSC-mediated pressure-induced TRI under moderate pressure and the intervention.
Methods :
We applied pressurized airwave to living retinas in vitro, and in photoreceptor rods and cones, we evaluated the pressure-associated activities of MSCs with FM 1-43 marker in five groups of mice, including wild-type mice, mice administered the energy booster levothyroxine (T4) and potassium iodide (I2), mice peritoneal-injected flupirtine and RN-1734, mutants of BK channel β-subunit, and mutants of TRPV4 channel.
Results :
We observed that moderate pressures of 0.3-3.3 psi could open MSCs in photoreceptors. The pressure effect was positively correlated with the pressure amplitude and affected by the frequency. The pressure increased the counts of fully activated photoreceptors (fPRs) and the b and I0 values of the exponential fitting curves of the pixel histogram of FM 1-43 in photoreceptors. In all experimental groups, pressure-induced responses were more intense in the peripheral retina, consistent with a higher peripheral pressure vulnerability. Oral administration of the energy boosters T4 and I2 and peritoneal injection of the BK agonist flupirtine and TRPV4 antagonist RN-1734 both decreased the intensity of pressure-related opening of MSCs, promoted low-level activities of MSCs in photoreceptors under pressure, and reduced the background opening of MSCs. TRPV4 mutation increased the background labeling of FM 1-43 but reduced pressure-related fPR counts in the peripheral retina. The retinas of mutant mice showed a nearly normal histological structure.
Conclusions :
The results indicate that raising the energy level, enhancing the hyperpolarizing MSCs, and suppressing the depolarizing MSCs have a neuroprotective effect, and the findings suggest novel mechanisms, strategies, and drugs likely applicable for treating traumatic retinal injury soon.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.