Article
Neurosciences
Meng- Zhao, Houting Lv, Na Yang, Guang-Hua Peng
Summary: The study investigated the mechanism of retinal photoreceptor degeneration by establishing a stable retinitis pigmentosa (RP) model. It was found that activation of mTOR may be associated with RP, and the use of mTOR inhibitor rapamycin improved retinal function and photoreceptor thickness and morphology, possibly by activating autophagy to protect retinal photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Natalia Martinez-Gil, Oksana Kutsyr, Agustina Noailles, Laura Fernandez-Sanchez, Lorena Vidal, Xavier Sanchez-Saez, Carla Sanchez-Castillo, Pedro Lax, Nicolas Cuenca, Antonio G. Garcia, Victoria Maneu
Summary: P2X7R and P2X4R play important roles in retinal diseases and their expression increases during disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hao-Yu Tsai, Henkie Isahwan Ahmad Mulyadi Lai, Zhang-Yuan Chen, Tai-Chi Lin, Winnie Khor, Wen-Chuan Kuo, Jia-Pu Syu, Ping-Hsing Tsai, Yi-Ping Yang, Yueh Chien, Shih-Jen Chen, De-Kuang Hwang, Shih-Hwa Chiou, Shih-Jie Chou
Summary: Inhibition of DUSP6 activity promotes autophagy flux and restores retinal damage caused by oxidative stress. DUSP6 inhibitor shows potential therapeutic effects in treating retinal degeneration.
Review
Pharmacology & Pharmacy
Janusz Blasiak, Kai Kaarniranta
Summary: Age-related macular degeneration (AMD) is an eye disease with poorly known pathogenesis and limited therapeutic options. Degradative autophagy (DA) is impaired in AMD, but emerging evidence suggests that secretary autophagy (SA) has a key role in AMD pathogenesis.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Merry Gunawan, Choonbing Low, Kurt Neo, Siawey Yeo, Candice Ho, Veluchamy A. Barathi, Anita Sookyee Chan, Najam A. Sharif, Masaaki Kageyama
Summary: This study showed that autophagy may not be an effective intrinsic protective mechanism for retinal damage induced by insults, including impaired proteasomal activity. Activation of autophagy beyond normal levels is required to alleviate the cytotoxic effect of proteasomal inhibition, suggesting the need for further research on the precise roles of different forms of autophagy in rescuing retinal neurons under various pathological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Guang-Ping Zou, Tao Wang, Jin-Xing Xiao, Xiao-Yu Wang, Li-Ping Jiang, Fang-Fang Tou, Zhi-Ping Chen, Xin-Hui Qu, Xiao-Jian Han
Summary: Age-related macular degeneration, a common cause of blindness in the elderly, is primarily attributed to oxidative stress and dysregulated autophagy in retinal pigment epithelium cells. Lactate has been found to act as a signaling molecule that protects against oxidative stress. This study aimed to investigate the protective effect of lactate against oxidative stress-induced retinal degeneration. The results showed that lactate alleviated oxidative stress-induced cell death and retinal degeneration by activating autophagy and preserving mitochondrial function.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Miae Oh, Jiah Yeom, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer, Young-Hee Lim
Summary: The study found that remofuscin extends the lifespan of Caenorhabditis elegans by activating the lysosome-to-nucleus pathway and increasing the expression levels of xenobiotic detoxification genes.
SCIENTIFIC REPORTS
(2022)
Article
Geriatrics & Gerontology
Nan Su, Uwe Hansen, Tanja Plagemann, Karin Gaeher, M. Dominik Leclaire, Jeannette Konig, Annika Hoehn, Tilman Grune, Constantin E. Uhlig, Nicole Eter, Peter Heiduschka
Summary: LF injection into the subretinal space of mice leads to activation and migration of microglial cells, increased expression of inflammatory cytokines, and gradual degradation of RPE cells. These features are consistent with those found in an aging retina, suggesting that LF injection could serve as a model for intermediate and late AMD.
Review
Biochemistry & Molecular Biology
Beatriz Villarejo-Zori, Juan Ignacio Jimenez-Loygorri, Juan Zapata-Munoz, Katharina Bell, Patricia Boya
Summary: Autophagy is a crucial quality control mechanism in cells, particularly in non-dividing cells like neurons. The retina, a light-sensitive tissue in the eye, is exposed to various stressors and requires autophagy for maintaining homeostasis. Understanding the role of autophagy in retinal function and eye diseases may lead to potential therapeutic strategies.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Cell Biology
Qitao Zhang, Feriel Presswalla, Robin R. Ali, David N. Zacks, Debra A. Thompson, Jason M. L. Miller
Summary: The autophagy inducer FLBZ shows promise as a potential therapeutic approach for dry AMD by increasing RPE autophagy flux, reducing lipid deposits, and promoting the production of energy sources.
Article
Ophthalmology
Nicholas P. Boyer, Debra A. Thompson, Yiannis Koutalos
Summary: The study investigated the contribution of all-trans retinal to the formation and stability of RPE lipofuscin in Rdh8(-/-) mice reared under cyclic-light conditions. Results showed that the levels of A2E and RPE lipofuscin accumulated faster in cyclic-light-reared mice compared to dark-reared mice, but the impact of increased all-trans retinal was modest. Additionally, moving cyclic-light-reared mice to darkness led to unexpected decreases in A2E levels, suggesting a potential therapeutic target for controlling A2E cytotoxicity.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Editorial Material
Neurosciences
Roberto Pinelli, Michela Ferrucci, Francesca Biagioni, Violet Bumah, Elena Scaffidi, Stefano Puglisi-Allegra, Francesco Fornai
Summary: Defective autophagy in the RPE is involved in AMD, and curcumin can protect RPE cells from damage induced by the autophagy inhibitor 3-MA by activating autophagy.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Geriatrics & Gerontology
Daniela Intartaglia, Giuliana Giamundo, Federica Naso, Edoardo Nusco, Simona Di Giulio, Francesco Giuseppe Salierno, Elena Polishchuk, Ivan Conte
Summary: This study confirms the therapeutic effect of inducing autophagy by inhibiting Ezrin in the treatment of retinitis pigmentosa. Drug-induced pulsatile inhibition of Ezrin can promote the clearance of disease-related aggregates, reduce cell death, and improve retinal morphology and function, ultimately leading to better preservation of vision.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Seon Beom Song, Woosung Shim, Eun Seong Hwang
Summary: This study examined the accumulation of lipofuscins in human fibroblasts under various stress conditions. The results showed that lipofuscins predominantly appear as granules that co-localize with autolysosomes in glucose-starved or replicative senescence cells, while they rarely manifest in the cytoplasm under oxidative stress induced by a doxorubicin pulse and chase. The findings suggest that autophagy activation triggers lipofuscin accumulation, and future treatments for lipofuscin-related diseases should consider autophagy activation.
MOLECULES AND CELLS
(2023)
Review
Neurosciences
Haydn Molcak, Kailun L. Jiang, Christopher J. J. Campbell, Joanne A. A. Matsubara
Summary: Age-related macular degeneration (AMD) is a complex and progressive inflammatory disease affecting the retina, with significant visual impairment. Purinergic signaling and its potential interactions with known contributors to AMD pathogenesis, such as complement dysregulation and inflammasome activation, have not been fully characterized. This review explores the role of purinergic signaling, ATP release, and their influence on AMD, aiming to improve our understanding of the disease mechanisms and develop effective treatment strategies.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Medicine, Research & Experimental
Katherine Shapiro, Wenbin Guo, Kody Armann, Natalie Pace, Bing Shen, Jicheng Wang, Jonathan Beckel, William de Groat, Changfeng Tai
Summary: The study found that low-frequency biphasic stimulation can induce poststimulation block, which is reversible, and the duration of stimulation required for inducing block increases with frequency. The results of this study provide an opportunity for the development of new neuromodulation devices.
Article
Physiology
Anand Mohapatra, Jialiang Chen, Jun Zhao, Yihua Zhong, Kody Armann, Bing Shen, Jicheng Wang, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: The study found that pudendal nerve stimulation had significant effects on bladder activity in cats, leading to underactive bladder. This animal model may be useful for investigating the mechanism of sacral neuromodulation in treating underactive bladder.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2021)
Article
Physiology
Jialiang Chen, Anand Mohapatra, Jun Zhao, Yihua Zhong, Bing Shen, Jicheng Wang, Zhijun Shen, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: This study demonstrated that superficial peroneal nerve stimulation (SPNS) could partially reverse bladder underactivity induced by prolonged pudendal nerve stimulation, suggesting a potential noninvasive neuromodulation therapy for treating this condition.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2021)
Article
Genetics & Heredity
Daniel A. Thorsteinsson, Vigdis Stefansdottir, Thor Eysteinsson, Sigridur Thorisdottir, Jon J. Jonsson
Summary: The study aimed to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, identifying 140 IRD patients with 70 undergoing genetic evaluation, revealing two-thirds with an identified genetic cause. Patients with retinitis pigmentosa in Iceland predominantly had RLBP1 gene variants, while X-linked retinoschisis (XLRS) patients had a possibly unique RS1 pathogenic variant.
Article
Physiology
Jialiang Chen, Yihua Zhong, Bing Shen, Jicheng Wang, Zhijun Shen, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: The purpose of this study was to investigate whether superficial peroneal nerve stimulation (SPNS) could improve nonobstructive urinary retention (NOUR) induced by prolonged pudendal nerve stimulation (PNS). The study found that continuous or intermittent application of SPNS significantly increased voiding efficiency and reduced postvoid residual volume. Furthermore, noninvasive SPNS applied by skin surface electrodes also improved NOUR. This study suggests that abnormal pudendal afferent activity may be a pathophysiological cause of NOUR in patients with Fowler's syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2022)
Article
Mathematical & Computational Biology
Yihua Zhong, Jicheng Wang, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: This modeling study aimed to develop a novel method to block nerve conduction using high frequency biphasic stimulation without generating initial action potentials. The simulation analysis demonstrated that step-increases in sub-threshold intensity during HFBS can successfully block axonal conduction.
JOURNAL OF COMPUTATIONAL NEUROSCIENCE
(2022)
Article
Ophthalmology
Stefan Broddi Danielsson, Andrea Garcia-Llorca, Hallur Reynisson, Thor Eysteinsson
Summary: This study assessed the vascular changes in Mitf mice carrying pathogenic variants and found an increase in retinal vessel diameter, indicating an increased demand for blood flow to the retina.
ACTA OPHTHALMOLOGICA
(2022)
Article
Physiology
Bing Shen, Jicheng Wang, Zhijun Shen, Jianan Jian, Khari Goosby, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation. It found that S2 dorsal root stimulation at 15 Hz and 1 T intensity was able to reverse the bladder underactivity induced by pudendal nerve stimulation.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2022)
Article
Engineering, Biomedical
Yihua Zhong, Xu Zhang, Jonathan Beckel, William C. de Groat, Changfeng Tai
Summary: A new axonal conduction model was used to analyze the interaction between intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency biphasic stimulation. The results show that the block duration can be shortened by increasing the HFBS intensity, and the block can be maintained if the intensity is above a certain threshold.
JOURNAL OF NEURAL ENGINEERING
(2022)
Article
Ophthalmology
Thor Eysteinsson, Andrea Garcia-Llorca, Andrea Angeli, Claudiu T. Supuran, Fabrizio Carta
Summary: In this study, the vasodilation properties of a series of carbonic anhydrase inhibitors (CAIs) on pre-contracted retinal arteries were investigated. The results showed that certain compounds exhibited potent vasodilation effects. However, the exact mechanism of action for CAIs as vasodilators needs further elucidation.
CURRENT EYE RESEARCH
(2022)
Review
Urology & Nephrology
Jialiang Chen, Yihua Zhong, Jicheng Wang, Bing Shen, Zhijun Shen, Jonathan Beckel, William de Groat, Christopher Chermansky, Changfeng Tai
Summary: This study demonstrates that pudendal nerve stimulation can improve vaginal lubrication and induce increases in vaginal pressure. It raises the possibility of developing a novel pudendal neuromodulation device to improve female sexual function after spinal cord injury.
JOURNAL OF SEXUAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Stephanie L. Daugherty, Keara M. Healy, Jonathan M. Beckel
Summary: ATP, released from the urothelium in response to bladder distension, plays a significant role in the sensory control of micturition. An experimental setup has been developed to directly measure ATP concentrations in the rodent urinary bladder, allowing for the study of the mechanisms controlling urothelial ATP release under different conditions.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Review
Geriatrics & Gerontology
Anirban Ganguly, Shachi Tyagi, Christopher Chermansky, Anthony Kanai, Jonathan Beckel, Mamoru Hashimoto, Kang Jun Cho, Michael Chancellor, Jonathan Kaufman, Naoki Yoshimura, Pradeep Tyagi
Summary: This article provides an overview of the diagnosis and treatment of lower urinary tract symptoms in older adults complicated by neurological changes, age-related decline in hepatic and renal clearance, and the propensity of adverse drug reactions. The use of intravesical antimuscarinics, which have a higher local concentration and lower systemic uptake compared to oral administration, has shown significant improvement in the treatment of neurogenic lower urinary tract symptoms. In addition, chemodenervation by onabotulinumtoxinA injection and liquid instillation have shown promise in treating idiopathic overactive bladder. Overall, individualized treatment tailored to the patient's overall health and risk tolerance is crucial.
Article
Biochemistry & Molecular Biology
Thor Eysteinsson, Andrea Garcia-Llorca, Arnar Oessur Hardarson, Daniela Vullo, Fabrizio Carta, Claudiu T. Supuran
Summary: Previous research has shown that carbonic anhydrase inhibitors (CAIs) can induce vasodilation in retinal arteriolar segments, but it is unclear which isoforms or mechanisms are responsible for this effect. In this study, four new CAIs that do not enter cell membranes but have high affinity for cytosolic and membrane-bound isoforms of CA were tested. None of these CAIs had a significant effect on arteriolar wall tension, while a membrane permeant CAI called benzolamide fully dilated all segments tested. This suggests that CAIs act as vasodilators through cellular mechanisms located in the cytoplasm of vascular cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Jianan Jian, Jonathan M. Beckel, William C. de Groat, Changfeng Tai
Summary: A new axonal conduction model that includes ion pump activity and allows for changes in ion concentrations is developed. The model successfully simulates action potential generation, propagation, and acute DC block, as well as the post-stimulation block phenomenon observed in animal studies. The study highlights the importance of ion concentrations and ion pump activity in post-stimulation block induced by long-duration DC stimulation.
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
(2023)