Immunology, particularly the immune regulation of autoimmune disease, and inflammation in degenerative and angiogenic diseases.
Retinal diseases, including age-related macular degeneration, diabetic retinopathy and uveoretintis.
Ocular drug delivery, in particular, intraocular drug delivery for retinal degenerative and angiogenic diseases.
I am interested in the cellular and molecular mechanisms involved in sight-threatening retinal diseases, including age-related retinal degeneration, diabetic retinopathy and uveitis. The research questions of my group centre on 1) the initiation and regulation of retinal inflammatory response during ageing and diabetes, 2) autoimmune response in uveitis, 3) the molecular mechanism of inflammation-mediated retinal neuronal degeneration, and 4) the link between chronic inflammation and the development of retinal angiogenesis or fibrovascular membrane. The goal is to use the knowledge for designing novel and rational strategies for immunotherapy.
Immunopathogenesis of age-related retinal degenerative disease
Age-related macular degeneration (AMD) is a disease in which the neuroretina, in particular, the macula, degenerates with age, resulting in loss of visual function. AMD is the leading cause of blindness in the elderly in developed countries. In the UK, AMD accounts for almost 50% of those registered blind or partially sighted.
Clinically, AMD begins with drusen depositions between retinal pigment epithelial (RPE) cells and choroid in the macular region (so-called age-related maculopathy, ARM). The disease can progress into two advanced forms causing substantial vision loss, "dry" and "wet". The "dry" AMD refers to central geographic atrophy resulting from apoptosis of RPE cells and subsequently, the death of photoreceptors in the macula. The "wet" form, also known as neovascular or exudative AMD, is caused by the retinal ingrowth of abnormal blood vessels from the choroid. Bleeding, leaking and scaring from new vessels damage photoreceptors resulting in rapid vision loss.
AMD is a multifactorial disease. Ageing, environmental factors (smoking, diet, sunlight exposure), and certain gene mutations all contribute to the disease development. Exactly, how these multiple factors work together leading to AMD is not known. Based on Herman's "free radical theory of ageing" (Harman. 1956), we hypothesize that AMD is an imbalance between free radical-induced retinal damage and the retinal repair/remodelling function. The key questions that we are addressing include (1) what are the immune responses to free-radical-mediated retinal injury during normal ageing? (2) why do such immune responses fail to restore retinal homeostasis in AMD?
Our studies in normal ageing retina have shown that retinal ageing is accompanied by a number of para-inflammatory changes (Xu et al. 2009), including microglial activation (Xu et al. 2009, Chen et al. 2009) and subretinal accumulation (Xu et al. 2008a, Xu et al. 2009), complement activation at the retina-choroidal interface (Chen et al. 2008, Xu et al. 2009), and choroidal inflammation (Chen et al. 2008, Xu et al. 2009).
Our results suggest that chronic stress (ageing in this case) induces para-inflammation in the ageing retina. The innate immune response, i.e. complement activation and microglial activation, constitutes the para-inflammatory response. In AMD, this protective para-inflammatory response is dysregulated, due to either genetic or epigenetic predisposition or environmental risk factors such as smoking (Chen and Xu. 2015).
Chronic inflammation and retinal angiogenesis or fibrovascular membrane
Retinal angiogenesis may occur in various pathological conditions such as retinal premature, diabetic retinopathy, AMD and uveoretinitis. The angiogenesis often develops into a fibrovascular membrane that severely damages vision due to leakage, haemorrhage or retinal detachment. Although ischemia has been considered as the primary stimulator for retinal angiogenesis, accumulating evidence suggests that inflammation may also play an important role, in particular in patients with AMD and chronic choroidal/retinal inflammation. Experimental studies in various models including hypoxia-induced and laser-induced choroidal neovascularisation have shown that inflammatory response is an important component of retinal angiogenesis or fibrosis. The aim of this part of our study is to uncover the link between chronic inflammation and retinal angiogenesis/fibrosis.
Inflammation in diabetic retinopathy
Diabetic retinopathy (DR) is the progressive degeneration of retinal vasculature and neurons resulting from long-term diabetes. During diabetes, hyperglycemia and metabolic intermediates are noxious stimuli to tissue cells. The immune system protects the host against the "danger" stimuli by mounting a pare-inflammatory response. However, compelling evidence suggests that para-inflammation in DR is disregarded and becomes detrimental chronic inflammation. We aim to understand how inflammation in DR is dysregulated. Particularly, we are interested in the impact of diabetes on immune cells, the link between inflammation (microglia/complement activation) and retinal neuronal and vascular degeneration.
Novel intraocular drug delivery for inflammatory/angiogenic retinal diseases
Intraocular drug delivery remains the biggest challenge for the management of chronic retinal diseases, such as AMD, DR, and uveoretinitis. In collaboration with scientists in biomaterials and pharmaceutics, and biotechnology industries we are developing safe and sustained intraocular drug delivery systems for the management of retinal inflammatory and angiogenesis diseases.
2018 - Present: Executive Editor of Current Eye Research
2018 - Present: Executive Editor of Experimental Eye Research
2018: Guest Editor of Oxidative Medicine and Cellular Longevity
2018 - Present: Executive Editor of Annals of Translational Medicine
2016 - Present: Editorial Board Member of Annals of Eye Science
2015 – Present: Editorial Board Member of Macrophage.
2014 – Present: Editorial Board Member of Scientific Reports.
2010 – 2018: Editorial Board Member of World Journal of Stem Cells (WJSC).
Invited presentations/lectures (Since 2013)
- The role of inflammation in microvascular dysfunction - a view from the retina. A*STAR, Institute of Molecular and Cell Biology, August 2018. Singapore.
- Innate Immune Activation in Neovascular Age-related Macular Degeneration. Shenzhen International Sumit Frurm on Ophthalmology and Visual Science. July 2018, Shenzhen, China
- Inflammation in diabetic retinopathy. Molecular Mechanisms for Eye Development & Ocular Pathogenesis and Beyond Symposium. 8-9th April 2018. Zhongshan Ophthalmic Center (ZOC) Guangzhou, China.
- Subretinal Inflammation in the ageing eye and in AMD. 10th Chinese Congress of Research in Vision and Ophthalmology (CCRVO2018). 12-15 April 2018, Changsha, China
- The role of inflammation in diabetes-induced retinal microvascular degeneration. British Microcirculation Society Conference (Keynote). 16-17 April 2018. Nottingham, UK.
- Taming inflammation for the management of retinal disease – what do we know, where do we go? Henan Eye Institute, 26-27th November 2017, China
- Metabolic control of microglial activation for the management of retinal degeneration. International Retinal Summit. 27-29 October 2017. Shenzhen, China.
- Immune Privilege in the ageing eye. July 2017, Xiamen University, China
- The role of STAT3 in diabetic retinopathy. The 9th Chinese Congress of Research in Vision and Ophthalmology. April 2017, Beijing, China.
- Para-inflammation, chronic inflammation and age-related macular degeneration. ARVO Annual Meeting. May 2017, Baltimore, USA.
- Metabolic control of microglial activation. ISER 2016 Biennial Meeting. Sept. 2016. Tokyo, Japan.
- Inflammation in age-related macular degeneration – what do we know about it? Sept. 2016. Zhongshan Ophthalmic Centre. Sun-Yat-Sen University. China.
- Molecular regulation of microglial activation in retinal degenerative disease. 5th Global Chinese Ophthalmic Conference/21st Congress of Chinese Ophthalmological Society. Sept. 2016, Suzhou, China.
- Dysregulated para-inflammation and age-related macular degeneration. 9th Internal Symposium on Uveitis. August 2016, Dublin, Ireland
- Para-inflammation – what is it and why might it be important? 2016 ARVO Annual Meeting. Seattle, USA
- Para-inflammation, the concept and its implications in age-related retinal diseases. Feb. 2016, University of Cologne, Germany.
- Para-inflammation, chronic inflammation and age-related macular degeneration. Danish Society of Immunology, November 2015, Copenhagen, Denmark.
- Deletion of SOCS3 in myeloid cells results in severe retinal inflammation and accelerated retinal angiogenesis in experimental autoimmune uveoretinitis. 5th International Uveitis Symposium, Oct. 2015, Chongqing, China.
- Taming inflammation for the management of retinal degenerative diseases. Xiangya Hospital, Central South University of China. Oct. 2015.
- Immune cell activation in diabetic retinopathy. European Association for Vision and Eye Research (EVER) 2015 annual meeting. October 2015. Nice, France.
- Retinal innate immune activation in healthy and disease. European Association for Vision and Eye Research (EVER) 2015 annual meeting. October 2015. Nice, France.
- Innate immune response in neovascular age-related macular degeneration. 7th Chinese Congress of Research in Vision and Ophthalmology. Aug. 2015. Shenyang, China.
- Regulation of retinal immune response in health and disease. Aug. 2015. Zhongshan Ophthalmic Center, China.
- Inflammation in diabetic retinopathy. May 2015. ThromboGenics NV. Leuven, Belgium
- Systemic immune activation in age-related macular degeneration. May 2015. National Eye Institute (NEI), NIH, USA.
- Innate Immune Activation in age-related macular degeneration. March 2015. Cambridge Neuroscience Spring School. The University of Cambridge. UK
- Immunology of retinal degenerative disease. Association for Ocular Pharmacology & Therapeutics Annual Meeting. Feb 2015. Charleston, SC, USA.
- In vivo non-invasive imaging of retina immune response. Pharmacology 2014, London. Dec. 2014. UK
- Retinal innate immune activation in health and disease. Optic Nerve Conference 2014. Obergurgl, December 2014. Austria.
- Dysregulated Para-inflammation in diabetic retinopathy. Eastern Finland University, Kuopio, November 2014. Finland.
- Taming the immune response for retinal health. Novaliq GmbH, Heidelberg, November 2014. Germany.
- Innate immune activation in neovascular age-related macular degeneration. ARVO Ocular Immunity, Autoimmunity and Inflammation Conference. October 2014. Fort Lauderdale, FL, USA.
- Dysregulated para-inflammation in the pathogenesis of age-related macular degeneration. European Association for Vision and Eye Research (EVER) 2014 annual meeting. October 2014. Nice, France.
- Innate immune activation and retinal angiogenesis. European Association for Vision and Eye Research (EVER) 2014 annual meeting. October 2014. Nice, France.
- Complement expression in retinal pigment epithelial cells is modulated by activated macrophages. 112th DOG Congress, September 2014. Leipzig, Germany.
- The role of myeloid-derived cells in inflammation-mediated retinal angiogenesis. ISER XXI Biennial Meeting. July 2014. San Francisco, USA.
- Microglial activation in the ageing eye. ARVO 2014 Annual Meeting. May 2014. Orlando, FL, USA.
- Inflammation in age-related macular degeneration. University of Birmingham. March 2014, UK
- Para-inflammation in retinal ageing and age-related macular degeneration. The Ageing Summit 2014. February 2014. London, UK
- Inflammation in age-related macular degeneration. Institute de la Vision. Oct 2013. Paris. France.
- Inflammation in retinal ageing and age-related retinal degeneration. 11th World Congress of Inflammation. September 2013. Natal, Brazil.
- Inflammation in retinal health and disease. June 2013. Wenzhou Medical University. China.
- Chronic inflammation and retinal angiogenesis. EURETINA Winter meeting. February 2013. Rome, Italy.
- Macrophages and retinal angiogenesis. Macula of Paris-7th International Congress on AMD. January 2013. Paris, France
- MED1012: Year 1-2 Medicine, Personal & Professional Development Portfolios.
- MED1021: Year 1 Medicine, Student Selected Component (module coordinator).
- BMS2016: Year 2 Biomedical Science “Immunobiology”.
- BMS3012: Year 3 Biomedical Science Research Projects.
- SCM8021: Master of Research, Molecular Medicine.
- SCM8059: Year 1 Postgraduate Research, Specialist Lecture Series in Vision and Vascular Science.
Research output: Contribution to journal › Article
Research output: Chapter in Book/Report/Conference proceeding › Chapter (peer-reviewed)
Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration
Research output: Contribution to journal › Article
Additional searchable ISSN (Electronic): 1552-5783
Association for Research in Vision and Ophthalmology Inc.
Scopus rating (2017): CiteScore 3.26 SJR 2.058 SNIP 1.222
Scopus rating (2017): CiteScore 3.56 SJR 2.04 SNIP 0.98
Additional searchable ISSN (Electronic): 1932-6203
Public Library of Science
Scopus rating (2017): CiteScore 3.01 SJR 1.164 SNIP 1.111
Additional searchable ISSN (Electronic): 1096-0007
Academic Press Inc.
Scopus rating (2017): CiteScore 3.28 SJR 1.449 SNIP 1.114
Additional searchable ISSN (Electronic): 1521-4141
Scopus rating (2017): CiteScore 3.59 SJR 2.206 SNIP 0.92
Activity: Consultancy types › KTP & Consultancy in kind