To test the hypothesis that imaging biomarkers are useful for evaluating in vivo rod photoreceptor cell responses to a mitochondrial protonophore. Methods Intraperitoneal injections of either the mitochondrial uncoupler 2,4 dinitrophenol (DNP) or saline were given to mice with either higher [129S6/eVTac (S6)] or lower [C57BL/6J (B6)] mitochondrial reserve capacities and were studied in dark or light. We measured: (i) the external limiting membrane-retinal pigment epithelium region thickness (ELM-RPE; OCT), which decreases substantially with upregulation of a pH-sensitive water removal co-transporter on the apical portion of the RPE, and (ii) the outer retina R1 (= 1/(spin lattice relaxation time (T1), an MRI parameter proportional to oxygen / free radical content. Results In darkness, baseline rod energy production and consumption are relatively high compared to that in light, and additional metabolic stimulation with DNP provoked thinning of the ELM-RPE region compared to saline injection in S6 mice; ELM-RPE thickness was unresponsive to DNP in B6 mice. Also, dark-adapted S6 mice given DNP showed a decrease in outer retina R1 values compared to saline injection in the inferior retina. In dark-adapted B6 mice, transretinal R1 values were unresponsive to DNP in superior and inferior regions. In light, with its relatively lower basal rod energy production and consumption, DNP caused ELM-RPE thinning in both S6 and B6 mice.

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Zenith award from the Alzheimer's Association (STB), the Tau Consortium/Rainwater Foundation (STB), as well as funds from Neurodegenerative Research Inc (GM) and the Secchia Family Foundation (NMK).We wish to acknowledge and thank Tessa Grabinski and Chelsey Yob for technical assistance as well as

Purpose The phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision. Methods In dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking. Results In light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil. Conclusions The sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

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Purpose To evaluate surgeon performance and intraoperative complication rates of cataract surgery after resumption of elective surgeries following the operating room (OR) shutdown from the coronavirus disease 2019 (COVID-19) pandemic. Subjective surgical experience is also evaluated. Methods This is a retrospective comparative study which analyzes cataract surgeries performed at an inner city, tertiary academic center. Cataract surgeries were categorized into Pre-Shutdown (January 1–March 18, 2020), and Post-Shutdown, for all cases which occurred after surgeries resumed (May 11–July 31, 2020). No cases were performed between March 19 and May 10, 2020. Patients undergoing combined cataract and minimally invasive glaucoma surgery (MIGS) were included, but MIGS complications were not counted as cataract complications. No other combined cataract-other ophthalmic surgeries were included. A survey was used to gather subjective surgeon experience. Results A total of 480 cases (n=306 Pre-Shutdown and n=174 Post-Shutdown) were analyzed. Although there was a higher frequency of complex cataract surgeries performed Post-Shutdown (5.2% vs 21.3%; p<0.00001), complication rates before versus after the shutdown were not statistically significant (9.2% vs 10.3%; p=0.75). Phacoemulsification was the step of cataract surgery in which residents were most concerned about when returning to the OR. Conclusion After the surgical hiatus due to COVID-19, significantly more complex cataract surgeries were reported and surgeons reported higher general anxiety level when first returning to the OR. Increased anxiety did not lead to higher surgical complications. This study provides a framework to understand surgical expectations and outcomes for patients whose surgeons faced a prolonged two-month hiatus from cataract surgery.

Background: Many studies on Alzheimer's disease (AD) focus solely on how neuronal proteins change in the brain, so little is known about what is happening to these same proteins in peripheral tissues. For example, it is known that tau is present within the human submandibular gland and that levels of some tau variants are inversely relate to Braak neurofibrillary tangle (NFT) stage. However, it is unclear if other neuronal proteins may also be detected in the submandibular gland and whether their levels are also disrupted. Such insights may provide new knowledge of the mechanisms of selective vulnerability and aid in developing better model systems and treatments. Methods: Submandibular glands were collected from human autopsy cases of AD (N¼17) and nondemented individuals (ND, N¼16). Biochemical and immunohistochemical methods were performed with markers for neuronal proteins including neurofilament, tyrosine hydroxylase (TH), and choline acetyl transferase (ChAT), in addition to select tau antibodies. Human brain samples of AD and ND cases were utilized as controls. Results: Biochemically, neurofilament, TH, and ChAT although present within the submandibular gland, did not appear to be altered by AD status, Braak NFT stage, nor correlated to tau levels. With respect to immunohistochemistry, neurofilament and TH were mainly within stromal nerve fascicles, while ChAT was mainly located within connective tissues proximal to blood vessels and ducts. Although neither neurofilament, TH, or ChAT had complete colocalization, all three did have some colocalization with select tau antibodies. Conclusions: These preliminary results demonstrate that neurofilament, TH, and ChAT can be detected within submandibular glands, although their levels do not appear to be altered based on AD status. Their co-localization with tau provides additional evidence that tau within the periphery is neuronal in nature.