Mutations in rod opsin, the visual pigment protein of rod photoreceptors, account for ≈15% of all inherited human retinal degenerations. However, the physiological and molecular events underlying the disease process are not well understood. One approach to this question has been to study transgenic mice expressing opsin genes containing defined mutations. A caveat of this approach is that even the overexpression of normal opsin leads to photoreceptor cell degeneration. To overcome the problem, we have reduced or eliminated endogenous rod opsin content by targeted gene disruption. Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form. Within months of birth, photoreceptor cells degenerated completely. Retinas from mice with a single copy of the opsin gene developed normally, and rods elaborated outer segments of normal size but with half the normal complement of rhodopsin. Photoreceptor cells in these retinas also degenerated but did so over a much slower time course. Physiological and biochemical experiments showed that rods from mice with a single opsin gene were ≈50% less sensitive to light, had accelerated flash-response kinetics, and contained ≈50% more phosducin than wild-type controls.

Retinal photoreceptors use the heterotrimeric G protein transducin to couple rhodopsin to a biochemical cascade that underlies the electrical photoresponse. Several isoforms of each transducin subunit are present in the retina. Although rods and cones seem to contain distinct transducin subunits, it is not known whether phototransduction in a given cell type depends strictly on a single form of each subunit. To approach this question, we have deleted the gene for the rod transducin α-subunit in mice. In hemizygous knockout mice, there was a small reduction in retinal transducin α-subunit content but retinal morphology and the physiology of single rods were largely normal. In homozygous knockout mice, a mild retinal degeneration occurred with age. Rod-driven components were absent from the electroretinogram, whereas cone-driven components were retained. Every photoreceptor examined by single-cell recording failed to respond to flashes, with one exception. The solitary responsive cell was insensitive, as expected for a cone, but had a rod-like spectral sensitivity and flash response kinetics that were slow, even for rods. These results indicate that most if not all rods use a single transducin type in phototransduction.

Purpose: To report the choroidal vascular flow area in eyes with central serous chorioretinopathy (CSC) compared with healthy subjects and unaffected fellow eyes using swept-source (SS) optical coherence tomography (OCT) angiography. Methods: Prospective case series of 19 eyes of 19 consecutive patients affected by CSC, compared with 15 unaffected fellow eyes and 20 eyes of 10 healthy subjects. Patients underwent SS-OCT angiography in order to evaluate the choroidal vascular flow area of choriocapillaris (CC) and deeper choroidal layers. Results: The choroidal vascular flow area was higher in eyes with CSC than in control eyes (53.4 ± 5.8% vs. 49.45 ± 8.16%; P = 0.0001). Within the choroid of CSC patients choroidal vascular flow area of the CC was significantly lower than the deeper level (50.97 ± 2.8% vs. 54.22 ± 6.3%; P = 0.025). There were no differences within the choroid of control eyes. The choroidal vascular flow area at the level of the CC was higher in the unaffected fellow eye (50.74 ± 0.9%; P = 0.019) than in control eyes. Choroidal vascular flow area of unaffected fellow eyes did not differ from CSC eyes (P = 0.17). The choroidal vascular flow area at the level of the CC was higher in the CSC eyes (P = 0.0009) compared with unaffected fellow eyes. Conclusions: Choroidal vascular flow area is larger in CSC eyes compared with control eyes. However, within the choroid of eyes with CSC, there might be some differences in flow area between CC and deeper choroidal levels. This difference might be secondary to a compensatory mechanism of the choroid.

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.