SAUR63 stimulates cell growth at the plasma membrane.

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion. Similarly, Arabidopsis thaliana SAUR63 was able to increase growth of various organs, antagonize PP2C.D5 phosphatase, and increase H+-ATPase activity. Using a gain-of-function approach to bypass genetic redundancy, we dissected structural requirements for SAUR63 growth-promoting activity. The divergent N-terminal domain of SAUR63 has a predicted basic amphipathic α-helix and was able to drive partial PM association. Deletion of the N-terminal domain decreased PM association of a SAUR63 fusion protein, as well as decreasing protein level and eliminating growth-promoting activity. Conversely, forced PM association restored ability to promote H+-ATPase activity and cell expansion, indicating that SAUR63 is active when PM-associated. Lipid binding assays and perturbations of PM lipid composition indicate that the N-terminal domain can interact with PM anionic lipids. Mutations in the conserved SAUR domain also reduced PM association in root cells. Thus, both the N-terminal domain and the SAUR domain may cooperatively mediate the SAUR63 PM association required to promote growth.

Macular Atrophy Affecting Visual Outcomes in Patients Undergoing Anti-VEGF Treatment in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: To explore how baseline macular atrophy (MA) affects visual acuity (VA) in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A retrospective, case control series. Patients were grouped into three cohorts based on baseline spectral-domain optical coherence tomography image findings: foveal MA, nonfoveal MA, and no MA. Outcomes were assessed at 1, 2, and 3 years following anti-VEGF therapy. RESULTS: No differences existed in MA growth between eyes with foveal and nonfoveal MA (0.89 mm2 [95% confidence interval (CI), 0.64-1.14] vs. 0.88 mm2 [95% CI, 0.72-1.05]) after adjusting for baseline lesion sizes at 3 years. Foveal MA patients lost an average of 19.4 ETDRS letters (95% CI, -30.8 to -8.0) after 3 years. Nonfoveal MA patients gained an average of 1.1 ETDRS letters (95% CI, -6.8 to 9.0), and patients without MA averaged a gain of 9.7 ETDRS letters (95% CI, 5.5-14.0). CONCLUSION: In patients with nAMD receiving anti-VEGF in routine clinical practice, presence of baseline foveal MA was associated with significant vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:68-75.].

Long-Term Assessment of Macular Atrophy in Patients with Age-Related Macular Degeneration Receiving Anti-Vascular Endothelial Growth Factor.

PURPOSE: Although intravitreal anti-vascular endothelial growth factor (VEGF) injection has become the mainstay treatment for neovascular age-related macular degeneration (nAMD), emerging studies suggest that anti-VEGF may be correlated with the development of macular atrophy (MA) in chronic therapy. The purpose of the current study is to determine the prevalence and progression of MA in nAMD treated with chronic anti-VEGF in a routine clinical practice. DESIGN: Retrospective cohort. PARTICIPANTS: Patients with nAMD who were previously treatment-naïve and treated with anti-VEGF at the Cole Eye Institute for at least 4 years. METHODS: This is chart review on anti-VEGF treated patients with nAMD with baseline and yearly follow-up spectral domain-OCT for at least 4 years. Retinal pigment epithelium subillumination analysis was used to automate identification of atrophy. Segmentation errors were manually corrected by 4 expert raters using a standardized grading protocol to quantify MA size. Patient baseline characteristics and treatment course were analyzed to identify predictive factors for the development of MA. MAIN OUTCOME MEASURES: MA growth rate and prevalence in cohorts with and without baseline atrophy. RESULTS: A total of 79 eyes from 66 patients (79.8±7.4 years, 63% were female) with nAMD and 4 years of follow-up with anti-VEGF injections were identified. The mean baseline visual acuity was 0.48±0.25 logarithm of the minimum angle of resolution (20/60 Snellen equivalent), and the mean final visual acuity was 0.48±0.49 logarithm of the minimum angle of resolution (20/44 Snellen equivalent, P = 0.23). The average number of injections was 19.8±9.8. MA was observed in 12.7% of eyes at baseline with an average annual growth rate of 0.7±0.5 mm2. In eyes without baseline MA, atrophy developed in 53.6% eyes by year 4 with a growth rate of 0.2±0.4 mm2 per year. Multiple linear regression analysis revealed that the progression of MA was positively correlated with age (R = 0.02, P = 0.009). CONCLUSIONS: More than half of patients with nAMD treated with anti-VEGF injections for 4 years developed new MA. Atrophy progression was most strongly correlated with age, which suggests that baseline disease characteristics may be more predictive of MA progression than cumulative anti-VEGF treatment.