Article
Biochemistry & Molecular Biology
Jang-Hyuk Yun, Da-Hye Lee, Han-Seok Jeong, Seung-Hoon Kim, Sang-Kyu Ye, Chung-Hyun Cho
Summary: This study demonstrates the importance of STAT3 activation in microglia in diabetic retinopathy, showing that it leads to pericyte apoptosis through increased TNF-alpha expression. Inhibiting STAT3 activation could be a potential therapeutic target for preventing pericyte loss in diabetic retinopathy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Physiology
Sarah Riemann, Matthias Kolibabka, Stephanie Busch, Jihong Lin, Sigrid Hoffmann, Norbert Gretz, Yuxi Feng, Paulus Wohlfart, Hans-Peter Hammes
Summary: Vascular dysfunction and vasoregression are characteristics of various inflammatory central nervous system disorders and inflammation-related retinal diseases. Activation of microglia and the humoral innate immune system play contributing roles. In this study, clodronate treatment led to an increase in activated CD74(+) microglia and prevented acellular capillaries and pericyte loss, indicating a shift towards induction of pleiotropic protective pathways supporting vasoprotection in neurovascular retinal diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aurora Mazzeo, Massimo Porta, Elena Beltramo
Summary: The complexity of retinal structure makes it difficult to describe the interactions between its composite cells. In this study, a commercially available human microglial cell line was characterized to study its susceptibility to inflammation and investigate the species-specific interactions between neuro-vascular retinal components. The researchers found that this cell line showed potential for investigating the events leading to diabetic retinopathy and suggested that co-culture models involving microvascular cells could enhance the understanding of the multifaceted interactions in the neurovascular unit.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Lei Tang, Chaoyang Zhang, Lixia Lu, Haibin Tian, Kun Liu, Dawei Luo, Qinghua Qiu, Guo-Tong Xu, Jingfa Zhang
Summary: This study found that in diabetic retinopathy, microglia were activated and migrated from the inner retina to the outer retina, leading to albumin leakage at the interaction site with damaged pericytes and endothelial cells. Melatonin was able to suppress microglial activation and maintain the integrity of the blood-retinal barrier by inhibiting the PI3K/Akt/Stat3/NF-κB signaling pathway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Isabella Palazzo, Lisa Kelly, Lindsay Koenig, Andy J. Fischer
Summary: In this study, the researchers investigated different cytokines, growth factors, cell signaling pathways, and damage paradigms that influence NFkB-signaling in the mouse retina. They found that exogenous TNF and IL1 beta can activate NFkB-signaling in Muller glia in undamaged retinas. They also discovered that TLR1/2 agonist indirectly activates NFkB-signaling in Muller glia, but this activation depends on the presence of microglia.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Endocrinology & Metabolism
Si-ru Niu, Jian-min Hu, Shu Lin, Yu Hong
Summary: Diabetic retinopathy is characterized by leakage and obstruction of retinal microvessels caused by diabetes. It can lead to vision impairment and blindness if left untreated. Pericyte-related diseases are considered important factors in its development, and exosomes may play a crucial role in the progression of the disease.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Isabella Palazzo, Levi J. Todd, Thanh V. Hoang, Thomas A. Reh, Seth Blackshaw, Andy J. Fischer
Summary: Muller glia (MG) in mammalian retinas are incapable of regenerating neurons after damage, whereas the MG in lower vertebrates regenerate functional neurons. Identification of cell signaling pathways and gene regulatory networks that regulate MG-mediated regeneration is key to harnessing the regenerative potential of MG. In this study, NFkB signaling was found to play a crucial role in regulating immune cell accumulation and suppressing the neurogenic potential of MG after damage. Inhibition of NFkB enhanced the reprogramming of MG into neuron-like cells. Additionally, TGF beta 2 signaling and suppression of NFI and Id transcription factors were coordinated with NFkB signaling to regulate MG-mediated regeneration.
Article
Neurosciences
Whitney A. Thiel, Zachary Blume, Diana M. Mitchell
Summary: This study found that microglia are primarily responsible for the clearance of dying cells in the developing zebrafish retina, while Muller glia also have a limited role in this process. In the absence of microglia, Muller glia significantly increase their uptake of apoptotic cells, with several of these cells localized with the early phagosome/endosome marker Rab5. Additionally, lysosomal staining also increases in Muller glia in the absence of microglia. These findings highlight the phagocytic capacity and compensatory functions of Muller glia, and emphasize the need to consider the effects of microglial deficiency or depletion on other glial cell types.
Article
Medicine, Research & Experimental
Mengyuan Fang, Wencui Wan, Qiuming Li, Weiwei Wan, Yang Long, Hongzhuo Liu, Xin Yang
Summary: The study aimed to evaluate the effects of Asiatic acid (AA) on the pathological processes of diabetic retinopathy (DR). Results showed that AA alleviated blood-retinal barrier breakdown and inflammation, while promoting M2 polarization in the retina of DR rats. In vitro assays confirmed the protective effects of AA on inner and outer BRB breakdown induced by high glucose and LPS-stimulated microglia cells. The study also demonstrated that AA weakened the TLR4/MyD88/NF-kappa B p65 signaling pathway, suggesting its potential as a candidate for DR treatment.
Article
Endocrinology & Metabolism
Christopher R. Starr, Assylbek Zhylkibayev, James A. Mobley, Marina S. Gorbatyuk
Summary: Diabetes, a metabolic disease, can lead to various health complications. Diabetic retinopathy (DR) affects millions of people worldwide and has complex mechanisms involving both neural and vascular components in the retina. This study identified changes in protein levels and O-glycosylation in the retinas of diabetic mice, providing important insights into the impact of diabetes on protein function and localization.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Samuel A. Mills, Andrew Jobling, Michael A. Dixon, Bang Bui, Kirstan A. Vessey, Joanna A. Phipps, Ursula Greferath, Gene Venables, Vickie H. Y. Wong, Connie H. Y. Wong, Zheng He, Flora Hui, James C. Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher
Summary: Local blood flow control within the central nervous system (CNS) is dependent on coordination between neurons, glia, and blood vessels. This study explored the role of microglia in retinal vasoregulation, showing that microglia actively participate in the neurovascular unit and contribute to vascular compromise during diabetic retinopathy. The findings suggest that aberrant microglial-vascular function may play a role in early vascular changes in diabetic retinopathy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Ying Chen, Andrea Schlotterer, Luke Kurowski, Lin Li, Marcus Dannehl, Hans-Peter Hammes, Jihong Lin
Summary: miR-124 plays a protective role in diabetic retinopathy by reducing vasoregression, glial activation, and inflammatory responses, and improving neuroretinal function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Maria Iribarne, David R. Hyde
Summary: This study investigated the role of microglia in zebrafish retinal regeneration after damage. The researchers found that acute and chronic damage led to different inflammation profiles and regeneration outcomes. Understanding the differences could provide valuable insights for improving therapeutic strategies for repairing injured mammalian tissues.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fei Yu, Michael L. Ko, Gladys Y-P Ko
Summary: Diabetic retinopathy is a chronic complication associated with diabetes and about 60% of type 2 diabetes patients will develop this condition. Research indicates that decreased miR-150 and upregulated ELK1 in the retina contribute to photoreceptor apoptosis, with the translocation of pELK1(T417) appearing to be a crucial step in diabetic insult-induced photoreceptor apoptosis.
Review
Ophthalmology
Xinran Qin, Haidong Zou
Summary: Diabetic retinopathy (DR) is a common complication of diabetes and the leading cause of blindness in the working-age population. Increased levels of serum lipopolysaccharides (LPS) are closely associated with the progression of DR, and LPS may contribute to vascular pathology and neurodegeneration in DR by disrupting the blood-retina barrier and dysregulating glial activation.
Review
Ophthalmology
Zhichao Wu, Erica L. Fletcher, Himeesh Kumar, Ursula Greferath, Robyn H. Guymer
Summary: Reticular pseudodrusen are distinct lesions in the subretinal space that have been increasingly recognized in association with age-related macular degeneration. Understanding their pathogenesis is crucial for understanding the processes driving vision loss in AMD.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Editorial Material
Genetics & Heredity
Samaneh Farashi, Zhichao Wu, Carla J. Abbott, Alice Pebay, Erica L. Fletcher, Robyn H. Guymer, Melanie Bahlo, Brendan R. E. Ansell
Summary: Reticular pseudodrusen (RPD) is a distinct phenotype associated with late-stage age-related macular degeneration (AMD), characterized by subretinal deposits. The genetic risk associations of RPD overlap with six established AMD-risk regions. Identifying the specific underlying genetic causes of RPD through adequate imaging methods can enhance our understanding of RPD pathophysiology.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Alice Brandli, Fay L. Khong, Roy C. K. Kong, Darren J. Kelly, Erica L. Fletcher
Summary: This study found the presence of fibrosis gene expression pathways in the laser induced CNV mouse model and suggested that anti-fibrotic treatments have the potential to reduce subretinal fibrosis in AMD.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Kirstan A. Vessey, Andrew Jobling, Mai X. Tran, Anna Y. Wang, Ursula Greferath, Erica L. Fletcher
Summary: Age-related macular degeneration (AMD) is a leading cause of vision loss, and recent evidence suggests that autophagy plays an important role in the progression of the disease. In this study, targeting autophagy was found to be effective in slowing dysfunction in a mouse model with features of early AMD. The treatments of metformin and trehalose showed potential in treating early AMD by enhancing autophagy pathways.
Article
Biochemistry & Molecular Biology
Candace Drysdale, Keunha Park, Kirstan A. Vessey, Xin Huang, Emily Caruso, Yihan Li, Joelyn Wong, James S. Wiley, Erica Fletcher, Robyn H. Guymer, Ben J. Gu
Summary: This study examined the membrane fluidity of peripheral blood leucocytes in patients with age-related macular degeneration (AMD) and in a mouse model lacking the P2X7 gene. The results showed decreased membrane fluidity in all types of leucocytes in late AMD patients. Pre-treatment with ATP increased membrane fluidity in monocytes and lymphocytes. P2X7 was found to mediate these ATP-driven increases in membrane fluidity, but without affecting pore formation or phagocytosis. The findings suggest a novel biological function of P2X7 in modulating membrane fluidity.
PURINERGIC SIGNALLING
(2022)
Review
Neurosciences
Josephine H. C. Wong, Jessica Y. W. Ma, Andrew I. I. Jobling, Alice Brandli, Ursula Greferath, Erica L. L. Fletcher, Kirstan A. A. Vessey
Summary: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the older population, characterized by drusen accumulation and pigmentary abnormalities. The death of the retinal pigment epithelium (RPE) and photoreceptors in late AMD result in vision impairment. The RPE is crucial for retinal health and communicates with the retinal and systemic immune environment. Dysfunction of the RPE and aberrant immune cell recruitment contribute to the pathogenesis of AMD, involving chronic inflammation and disease progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Ophthalmology
Erica L. Fletcher, Michael A. Dixon, Samuel A. Mills, Andrew I. Jobling
Summary: Diabetic retinopathy is the most feared complication for those with diabetes. Recent studies have shown that a range of cellular changes occur in the retina from an early stage of diabetes, including a loss of vasoregulation in response to changes in neural activity. Retinal immune cells, microglia, play an important role in mediating vasoconstriction. These findings highlight the significance of early changes in vascular regulation to the progression of diabetic retinopathy.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Dongmao Wang, Paul Trevillian, Stephen May, Peter Diakumis, Yanyan Wang, Deb Colville, Melanie Bahlo, Una Greferath, Erica Fletcher, Barbara Young, Heather G. Mack, Judy Savige
Summary: Scalp-Ear-Nipple syndrome, caused by pathogenic KCTD1 variants, is characterized by scalp defect, prominent ears, and rudimentary breasts. This study found further clinical associations in the eye and kidney.
OPHTHALMIC GENETICS
(2023)
Article
Anatomy & Morphology
Hallur Reynisson, Michael Kalloniatis, Erica L. Fletcher, Mohit N. Shivdasani, Lisa Nivison-Smith
Summary: A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. This study assessed the relationship between Muller cell dysfunction and retinal neuron subpopulations in late-stage retinal degeneration, finding that glia-neuronal alterations play a significant role. These findings highlight the importance of further research and intervention development in this field.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Ophthalmology
Ursula Greferath, Erica Fletcher, Judy Savige, Heather G. Mack
Summary: Retinal drusen are uncommon in IgA nephropathy, but they resemble drusen found in age-related macular degeneration. The IgA-staining deposits in the drusen are likely related to systemic deposition of IgA. The nature of cystic spaces in the drusen is still unknown. Further research on the retinas of people with glomerulonephritis is recommended.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2024)
Article
Geriatrics & Gerontology
Jessica Y. W. Ma, Ursula Greferath, Josephine H. C. Wong, Linda J. Fothergill, Andrew I. Jobling, Kirstan A. Vessey, Erica L. Fletcher
Summary: This study investigated the changes in the retinal pigment epithelium (RPE) of C57BL/6J mice with age. The RPE structure was found to change, with increased cell size, loss of nuclei, and altered tight junctions in the peripheral retina. The study also revealed impairments in phagocytosis and autophagy processes in the aged RPE tissue, suggesting a contribution to RPE dysfunction and age-related macular degeneration (AMD) development.
NEUROBIOLOGY OF AGING
(2023)
Meeting Abstract
Ophthalmology
Quan Findlay, Ben Gu, Andrew Jobling, Erica Fletcher, Robyn Guymer
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2022)
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)