Article
Ophthalmology
Jung-Tae Kim, Ji-Ho Jun, Sung-Chul Lee, Min-Woo Lee
Summary: This study aimed to analyze the retinal microvasculature and choriocapillaris in different stages of dry age-related macular degeneration (AMD) and identify factors associated with their microvasculature. The results showed that the retinal microvasculature and choriocapillaris tended to become more impaired as the AMD stage progressed. Age was significantly associated with microvasculature impairments in all layers, and hypertension was significantly associated with impairments of the deep capillary plexus microvasculature and choriocapillaris.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Alessandro Arrigo, Alessia Amato, Costanza Barresi, Emanuela Aragona, Andrea Saladino, Adelaide Pina, Francesca Calcagno, Francesco Bandello, Maurizio Battaglia Parodi
Summary: In patients with age-related macular degeneration, degeneration of choriocapillaris and thinning of Sattler layer are early biomarkers for the onset of macular neovascularization.
OPHTHALMOLOGY AND THERAPY
(2022)
Review
Medicine, General & Internal
Sarah Hammadi, Nikolaos Tzoumas, Mariantonia Ferrara, Ingrid Porpino Meschede, Katharina Lo, Claire Harris, Majlinda Lako, David H. Steel
Summary: The complement system is essential for the body's defense against pathogens, but dysregulation can lead to diseases such as age-related macular degeneration (AMD). Complement activation occurs in various parts of the eye, including the choriocapillaris and the subretinal and retinal pigment epithelium spaces. The barrier of Bruch's membrane impedes complement protein diffusion and its dysfunction contributes to AMD pathogenesis. This review examines the structure of Bruch's membrane, its age-related changes, and the potential of different delivery routes for complement inhibitors in treating AMD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Ophthalmology
Assaf Hilely, Adrian Au, K. Bailey Freund, Anat Loewenstein, Eric H. Souied, Dinah Zur, Riccardo Sacconi, Enrico Borrelli, Enrico Peiretti, Claudio Iovino, Yoshimi Sugiura, Abdallah A. Ellabban, Jordi Mones, Nadia K. Waheed, Sengul Ozdek, Duygu Yalinbas, Sarah Thiele, Luisa Salles de Moura Mendonca, Mee Yon Lee, Won Ki Lee, Pierre Turcotte, Vittorio Capuano, Meryem Filali Ansary, Usha Chakravarthy, Albrecht Lommatzsch, Frederic Gunnemann, Daniel Pauleikhoff, Michael S. Ip, Giuseppe Querques, Frank G. Holz, Richard F. Spaide, SriniVas Sadda, David Sarraf
Summary: This study evaluated the patterns of subretinal fluid in eyes with non-neovascular AMD and found that SRF may be a result of RPE decompensation and RPE pump failure.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Young Gun Park, Yong Soo Park, In-Beom Kim
Summary: Age-related macular degeneration (AMD) is a complex disease characterized by neovascularization or geographic atrophy. The complement system plays a crucial role in AMD and has become a therapeutic target. Further research is needed to fully understand the mechanism of complement disease propagation in AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Marco Nassisi, Tudor Tepelus, Giulia Corradetti, Srinivas R. Sadda
Summary: The study demonstrates a significant correlation between choriocapillaris flow alterations and scotopic macular sensitivity in patients with early or intermediate AMD. Furthermore, it reveals the associations between FD3mm, FD6mm, and sMS.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Medicine, General & Internal
Jackson Scharf, Giulia Corradetti, Federico Corvi, SriniVas Sadda, David Sarraf
Summary: The advent of optical coherence tomography angiography (OCTA) has significantly advanced our understanding of the choriocapillaris in age-related macular degeneration (AMD), but further research and analysis of techniques for analyzing choriocapillaris images are needed.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Andrea P. Cabrera, Jonathan Stoddard, Irene Santiago Tierno, Nikolaos Matisioudis, Mahesh Agarwal, Lauren Renner, Neha Palegar, Martha Neuringer, Trevor McGill, Kaustabh Ghosh
Summary: The study found differences in the characteristics of choroidal endothelial cells in young and old monkey eyes, with cells in older eyes being stiffer and more susceptible to complement activation-induced damage. These differences may be related to the activities of the mechanical structure regulators Rac and Rho in the cells. These findings offer new mechanistic insights into choroidal vascular loss in early AMD and warrant further investigation for translational potential.
JOURNAL OF PATHOLOGY
(2022)
Review
Ophthalmology
Shenouda Girgis, Lawrence R. Lee
Summary: Age-related macular degeneration is a global disease with a significant social impact, and the treatment of neovascular AMD has been revolutionized by the advent of anti-VEGF therapy. Currently, investigations are being conducted for possible therapeutic options for dry AMD. Various treatments, including complement pathway inhibitors, visual cycle modulators, antioxidative therapy, gene therapy, and stem cell therapy, are undergoing clinical trials. Two intravitreal anti-complement factors have shown promising results in reducing the growth of geographic atrophy.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Angela Armento, Marius Ueffing, Simon J. Clark
Summary: Age-related macular degeneration (AMD) is a complex disease with genetic, aging, and lifestyle factors all playing a role in its onset and progression. Therapeutic attempts targeting the complement system have not been successful, highlighting the complexity of AMD beyond genetic factors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Niloofar Piri, Henry J. Kaplan
Summary: AMD is a progressive degenerative disease that severely affects central vision in people over age 50, impacting their ability to read, write, drive, and recognize faces. The disease is complex and multifactorial, involving age, genetics, and environmental factors. The role of complement system in the development of AMD is reviewed. Understanding the pathophysiology of AMD and its risk factors is crucial for drug discovery.
Article
Biochemistry & Molecular Biology
Fiona Cunningham, Sabrina Cahyadi, Imre Lengyel
Summary: The study suggests that changes in zinc concentration may directly impact fenestrae formation, and raising zinc levels may help restore the choriocapillaris fenestration, improving nutrient flow and waste clearance in AMD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Serena Fragiotta, Luca Scuderi, Clemente Maria Iodice, Daria Rullo, Mariachiara Di Pippo, Elisa Maugliani, Solmaz Abdolrahimzadeh
Summary: This narrative review explores the molecular and structural changes in the choroid during aging and AMD, and provides an overview of multimodal imaging techniques for visualizing choroidal modifications. Recent research has revealed a mechanistic link between high-risk genetic loci for AMD and mast cell recruitment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Prem N. Patel, Parth A. Patel, Matthew R. Land, Ibrahim Bakerkhatib-Taha, Harris Ahmed, Veeral Sheth
Summary: Age-related macular degeneration (AMD) is a common cause of vision loss in elderly individuals. The pathophysiology of dry AMD is associated with key proteins in the complement cascade, providing potential therapeutic targets. Early intervention may prevent disease progression.
Article
Medicine, General & Internal
Jonathan B. Lin, Stylianos Serghiou, Joan W. Miller, Demetrios G. Vavvas
Summary: Complement dysregulation is observed in early/intermediate nonexudative AMD, but not in patients with geographic atrophy. These findings provide insights into the mechanism of AMD and inform future clinical trials.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Ophthalmology
Andrew P. Voigt, Nathaniel K. Mullin, Edwin M. Stone, Budd A. Tucker, Todd E. Scheetz, Robert F. Mullins
Summary: Gene expression studies provide valuable insights into cell function, and with the advancement of single-cell RNA sequencing technology, researchers are able to achieve unparalleled resolution in observing gene expression at the level of individual cells. This technology has been widely adopted in vision research, leading to significant discoveries and advancements in understanding retinal physiology and disease.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Chemistry, Medicinal
Alicia Arranz-Romera, Maria Hernandez, Patricia Checa-Casalengua, Alfredo Garcia-Layana, Irene T. Molina-Martinez, Sergio Recalde, Michael J. Young, Budd A. Tucker, Rocio Herrero-Vanrell, Patricia Fernandez-Robredo, Irene Bravo-Osuna
Summary: The study evaluated the sustained delivery effect of PLGA/VitE microspheres loaded with neurotrophic factors on the migration of retinal cells and the survival of RGCs, demonstrating a positive impact on RPE cell migration and high cell viability in vitro.
Review
Cell Biology
Andrew E. Pouw, Mark A. Greiner, Razek G. Coussa, Chunhua Jiao, Ian C. Han, Jessica M. Skeie, John H. Fingert, Robert F. Mullins, Elliott H. Sohn
Summary: This review highlights the crucial role of the extracellular matrix (ECM) in maintaining normal physiologic functions and regulating processes such as angiogenesis and intraocular pressure in the eye. Various pathways and key factors related to ECM in the eye are discussed, along with alterations contributing to disease states like wound healing, diabetes-related complications, and age-related macular degeneration.
Article
Ophthalmology
Timothy M. Boyce, S. Scott Whitmore, Katayoun Varzavand, Stephen R. Russell, Elliott H. Sohn, James C. Folk, Edwin M. Stone, Ian C. Han
Summary: Patients with ADNIV have a high lifetime risk of severe vision loss, with tractional retinal detachment being an important risk factor for poor vision.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Budd A. Tucker, Erin R. Burnight, Cathryn M. Cranston, Mallory J. Ulferts, Meagan A. Luse, Trudi Westfall, C. Anthony Scott, Autumn Marsden, Katherine Gibson-Corley, Luke A. Wiley, Ian C. Han, Diane C. Slusarski, Robert F. Mullins, Edwin M. Stone
Summary: A study identified a genetic mutation in the MAK gene leading to retinitis pigmentosa, and explored the feasibility of using a viral gene augmentation strategy for treatment.
Letter
Clinical Neurology
Lucy P. Evans, Katherine N. Gibson-Corley, Robert F. Mullins, Budd A. Tucker, Amy Trent, Edwin M. Stone, Karra A. Jones
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Review
Ophthalmology
Nathaniel K. Mullin, Andrew P. Voigt, Jessica A. Cooke, Laura R. Bohrer, Erin R. Burnight, Edwin M. Stone, Robert F. Mullins, Budd A. Tucker
Summary: Advancements in molecular genetic analysis have greatly improved our understanding of inherited retinal diseases, though there is still a significant portion of patients without molecular diagnoses. Variants that do not obviously disrupt exonic codon sequences may exert pathogenic effects through gene expression and transcript-level mechanisms.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Oncology
Kelly Mulfaul, Nathaniel K. Mullin, Joseph C. Giacalone, Andrew P. Voigt, Melette DeVore, Edwin M. Stone, Budd A. Tucker, Robert F. Mullins
Summary: Activation of the alternative complement pathway is a crucial event in the development of age-related macular degeneration (AMD). Uncontrolled complement activation leads to the formation of the membrane attack complex (MAC). This study demonstrates that reduced levels of complement factor H (FH) in the choroid can contribute to MAC deposition on choroidal endothelial cells (CECs), while overexpression of FH can protect against MAC deposition. These findings highlight the importance of local FH production in preventing MAC deposition in AMD.
JOURNAL OF PATHOLOGY
(2022)
Article
Ophthalmology
Lola P. Lozano, Budd A. Tucker, Connie J. Hinz, H. Culver Boldt, Elaine M. Binkley
Summary: Von Hippel-Lindau (VHL) disease is a rare inherited cancer syndrome that leads to the development of tumors in multiple systems. This case report highlights the importance of being aware that rare diagnoses can co-exist, as seen in a patient with both retinopathy of prematurity (ROP) and VHL.
CASE REPORTS IN OPHTHALMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ian C. Han, Luke A. Wiley, Dalyz Ochoa, Mallory J. Lang, Brynnon E. Harman, Katie M. Sheehan, Robert F. Mullins, Edwin M. Stone, Budd A. Tucker
Summary: In this study, a novel Pde6b-deficient rat model was generated using CRISPR-Cas9 genome editing. The model exhibited rapid photoreceptor degeneration and adeno-associated viral vectors were successfully manufactured to drive human PDE6B expression. Subretinal gene therapy using these vectors was able to delay photoreceptor loss in the rat model.
Article
Cell Biology
Guillermo L. Lehmann, Michael Ginsberg, Daniel J. Nolan, Cristina Rodriguez, Jose Martinez-Gonzalez, Shemin Zeng, Andrew P. Voigt, Robert F. Mullins, Shahin Rafii, Enrique Rodriguez-Boulan, Ignacio Benedicto
Summary: A2M, a protease inhibitor, is found to be expressed in endothelial cells of the human eye choroid. The expression of A2M is induced by retinal pigment epithelium (RPE)-conditioned medium, with VEGF-A playing a key role. Furthermore, the inhibition of A2M leads to the restoration of gelatinase activity in culture supernatants. This study provides important insights into the alterations in choroidal ECM and visual function due to dysfunctional RPE or choroidal blood vessels.
Article
Biotechnology & Applied Microbiology
Luke A. Wiley, Timothy M. Boyce, Emily E. Meyering, Dalyz Ochoa, Katie M. Sheehan, Edwin M. Stone, Robert F. Mullins, Budd A. Tucker, Ian C. Han
Summary: Adeno-associated virus (AAV)-mediated gene therapy has the potential to treat retinal degenerative diseases, but recent evidence of AAV-associated inflammation has raised concerns. This study characterizes the severity and distribution of AAV-induced inflammation in rats, testing five different AAV vectors and three different routes of ocular delivery. The results show that AAV2 and AAV6 induce the most inflammation, with AAV6 causing the highest levels when delivered suprachoroidally. AAV8 and AAV9 induce minimal inflammation. These findings highlight the importance of considering ocular inflammation when developing gene therapy strategies.
HUMAN GENE THERAPY
(2023)
Article
Medicine, Research & Experimental
Nathaniel K. Mullin, Andrew P. Voigt, Miles J. Flamme-Wiese, Xiuying Liu, Megan J. Riker, Katayoun Varzavand, Edwin M. Stone, Budd A. Tucker, Robert F. Mullins
Summary: Variants in the high copy number mitochondrial genome can disrupt organelle function and lead to severe multisystem disease. Heteroplasmy, the uneven distribution of abnormal mtDNA molecules in different cells and tissues, contributes to the wide range of manifestations observed in patients with mitochondrial disease. This study reveals the nonrandom nature of mitochondrial variant distribution in human mitochondrial disease, highlighting its importance for understanding pathogenesis and developing treatments.
Article
Ophthalmology
He-Yan Li, Li Dong, Xu-Han Shi, Rui-Heng Zhang, Wen-Da Zhou, Hao-Tian Wu, Chu-Yao Yu, Yi-Tong Li, Yi-Fan Li, Jost B. Jonas, Wen-Bin Wei, Yue-Ming Liu
Summary: This study aimed to examine the intraocular tolerability of cetuximab when applied intravitreally, and its effect on axial elongation. The results showed that intravitreal injections of cetuximab could reduce axial elongation in a dose-dependent and number of treatment-dependent manner, without causing intraocular toxic effects.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
James D. Cole, John A. McDaniel, Joelle Nilak, Ashley Ban, Carlos Rodriguez, Zuhaad Hameed, Marta Grannonico, Peter A. Netland, Hu Yang, Ignacio Provencio, Xiaorong Liu
Summary: Aniridia is a panocular condition characterized by the loss of iris, caused mainly by mutations in the PAX6 gene. This study assessed the effects of Pax6-haploinsufficiency on retinal morphology and vision in Pax6Sey mice. The results showed elevated intraocular pressure and declining visual acuity in Pax6Sey mice, along with local retinal damage and a possible neuroinflammatory response.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Subao Jiang, Ning Xia, Francesco Buonfiglio, Elsa W. Boehm, Qi Tang, Norbert Pfeiffer, Dominik Olinger, Huige Li, Adrian Gericke
Summary: This study found that a high-fat diet induces endothelial dysfunction in the ophthalmic artery, leading to impaired vascular function in the eye. The high-fat diet triggers oxidative stress and involves RAGE and NOX2.
EXPERIMENTAL EYE RESEARCH
(2024)
Review
Ophthalmology
Mala Upadhyay, Vera L. Bonilha
Summary: The sodium iodate (NaIO3) model is a valuable tool in studying dry AMD and evaluating the retinal structure. Through extensive research, it has been found that the death of RPE cells caused by NaIO3 injection is closely related to vision loss in patients with dry AMD. Therefore, studying NaIO3 can provide insights into the mechanisms of RPE and photoreceptor cell death and contribute to understanding RPE degeneration in AMD.
EXPERIMENTAL EYE RESEARCH
(2024)
Article
Ophthalmology
Vicki Chrysostomou, Katharina C. Bell, Sze Woei Ng, Samyuktha Suresh, Gayathri Karthik, Marion Millet, Yingying Chung, Jonathan G. Crowston
Summary: We present a new experimental model for inducing retinal ganglion cell (RGC) dysfunction and degeneration in mice. This model allows for the reliable induction of RGC dysfunction and loss, with the resilience of the optic nerve being dependent on the age of the animal. The time-defined nature of the functional and structural changes observed in this model will facilitate the study of glial responses and the evaluation of neuroprotective treatments after intraocular pressure (IOP) injury.
EXPERIMENTAL EYE RESEARCH
(2024)