Carbonic anhydrase inhibitors(University of Wollongong)

Presenting a case of peripapillary retinoschisis in a patient with glaucomatous optic neuropathy that resolved after changing therapy from topical bimatoprost to timolol/dorzolamide.

A 70-year-old female who presented for a second opinion for peripapillary retinoschisis in the left eye.

The patient’s visual acuity was 20/25 and 20/30 in the right and left eyes, respectively. Dilated fundoscopy revealed posterior vitreous detachment (PVD) of the left eye, temporal cupping with a superotemporal notch of the left optic nerve, and bilateral macular drusen and pigmentary changes of the retinal pigment epithelium (RPE). Optical coherence tomography of the macula of the left eye showed a PVD, drusen, and peripapillary retinoschisis extending to and involving the fovea. Topical prostaglandin analogue eye drop was discontinued and replaced by dorzolamide/timolol. The peripapillary retinoschisis resolved after medication change over the following 48 months and has not recurred.

We present a case of peripapillary retinoschisis in a phakic patient that developed during treatment with a topical prostaglandin analogue. The schisis resolved after switching the prostaglandin analogue to a topical carbonic anhydrase inhibitor. We suggest that the prostaglandin may have had a role in initiating peripapillary retinoschisis associated with glaucomatous optic neuropathy and that carbonic anhydrase inhibitors are a potential treatment for this condition.

Cyanobacteria achieve highly efficient photosynthesis using a CO 2 -concentrating mechanism relying on specialized Type I (NDH-1) complexes. Among these, NDH-1 3 and NDH-1 4 catalyze redox-coupled hydration of CO 2 to bicarbonate, supporting carbon fixation in carboxysomes. The mechanism of coupling electron transfer to CO 2 -hydration by these variant NDH-1 complexes remains unknown. We engineered a Synechococcus PCC7942 strain that expresses exclusively the high flux/low affinity NDH-1 4 complex, enabling the observation of the coupling of CO 2 hydration to cyclic electron flow in isolation from the other NDH-1 isoforms normally present in cells. We found that inhibition of the CupB protein by the carbonic anhydrase inhibitor ethoxzolamide (EZ) suppressed CO 2 uptake, slowed photosystem I rereduction, and abolished proton pumping as probed by acridine orange fluorescence. These effects were absent in strains lacking Cup proteins, confirming specificity. The results demonstrate that CO 2 hydration and electron transfer through NDH-1 4 are tightly coupled via proton translocation across the thylakoid membrane. These findings provide direct evidence for the bidirectional interaction in bioenergetic coupling between the plastoquinone reduction and the CO 2 uptake at the distal Zn-site over a span of ~150 Å and support a proton-removal hypothesis involving the proton transfer pathways from the Zn-site of CO 2 hydration to an energetically coupled proton loading site evolutionarily repurposed from the ancestral proton pumping mechanism to enable energetic CO 2 uptake.