Scopus Author ID: Heping Xu  

Research Interests:

Immunology, particularly (1) immune regulation in ageing and age-related diseases, (2) neuron-immune system interaction, and (3) inflammation in degenerative and angiogenic diseases.

Retinal diseases, including age-related macular degeneration, diabetic retinopathy, and uveoretinitis.  

Ocular drug delivery, in particular, intraocular drug delivery for retinal diseases.  

The full list of publications from my group can be found at GoogleScholar or ResearchGate.

I am interested in the cellular and molecular mechanisms involved in sight-threatening retinal diseases, including age-related retinal degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosia (RP) and uveitis. The research questions of my group centre on 1) the initiation and regulation of retinal immune response under normal ageing and disease conditions, 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 fibrosis. The goal is to use the knowledge for designing novel and rational strategies for therapy.

Immunopathogenesis of age-related retinal degenerative disease

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 dysfunction 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 scarring 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 disease development. Exactly, how these multiple factors work together leading to AMD is unknown. We hypothesise that AMD is an imbalance between age-mediated retinal damage and the retinal repair/remodelling function. The key questions that we are addressing include (1) what are the immune responses to age-mediated retinal injury during normal ageing? (2) why do such immune responses fail to restore retinal homeostasis in AMD?

We have found that ageing not only accumulates oxidative stress, but also alters a number of immune checkpoint molecules in the retina, which put the retina at risk of developing various degenerative diseases (Chen et al. Prog Ret Eye Res. 2019). A para-inflammatory response, characterised by mild complement activation and microglial activation, exists in the ageing retina to maintain homeostasis (Xu et al. Prog Ret Eye Res. 2009). 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. J Leuko Biol. 2015).  

Chronic inflammation and retinal angiogenesis or fibrovascular membrane

Retinal angiogenesis may occur in various pathological conditions such as retinal premature, DR, 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 (Little et al. EBiomedicine, 2018). The aim of this part of our study is to uncover the link between chronic inflammation and retinal angiogenesis/fibrosis. We are currently focusing on the cellular sources and molecular pathways involved in retinal angiogenesis and 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 (Xu and Chen. Vis Res. 2017). We aim to understand how inflammation in DR is dysregulated. Particularly, we are interested in understanding 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 (Kaarniranta et al. Adv Drug Deliv Rev. 2018; Akhtar-Schafer et al. EMBO Mol Med. 2018). 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.

Editorial Services

2022 - Present: Editorial Board Member of Journal of Ocular Pharmacology and Therapeutics

2021 - Present: Associate Editor of Frontiers in Ophthalmology (section of Inflammatory Eye Disease)

2019: Guest Editor of Frontiers in Immunology

2019 - Present: Editor Board Member of Current Molecular Pharmacology

2018 - Present: Executive Editor of Current Eye Research

2017 - 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

2014 – Present: Editorial Board Member of Scientific Reports.

2010 – 2018: Editorial Board Member of World Journal of Stem Cells (WJSC).

Invited presentations/lectures (Since 2015)

1. Neuron-microglia interaction in retinal health and disease. 15th International Ocular Inflammation Society Congress (IOIS), Kaosheng, Taiwan, November 2019. (Modulator, Invited speaker)
2. Immune regulation in retinal health and disease. Shenzhen Eye Immunology Conference. ShenZhen University,  November 2019, China. (Invited speaker)
3. Neuron-microglial interaction and retinal degeneration. International Retina Summit. November 2019, Nansha, Guangzhou, China. (Invited speaker)
4. Microglial activation and breakdown of the blood-retinal barrier. 7th International Uveitis Congress. August 2019, Zhengzhou, China (Invited speaker and Modulator)
5. The role of microglia in the breakdown of blood-retina barrier. ARVO 2019 Annual Meeting. May 2019, Vancouver, Canada. (Invited speaker and Modulator)
6. Immune suppression as a strategy for the management of ocular angiogenic diseases. 14th Scientific Meeting of Association for Ocular Pharmacology & Therapeutics (AOPT). March 2019, New Orleans, USA. (Invited speaker and Modulator)
7. Immune regulation in the ageing retina. Italian Chapter of ARVO.  February 2019,  Catania, Italy. (Key Note Speaker)
8. Immune defense, inflammation in human health and disease.  Shanghai Ocean University. February 2019, China. (Invited Lecture)
9. Complement activation at the retina-choroidal interface. ISER 2018 meeting. Belfast, UK (Programme leader, Modulator, Invited Speaker)
   
10. The role of inflammation in microvascular dysfunction - a view from the retina. A*STAR, Institute of Molecular and Cell Biology,  August 2018. Singapore. (Invited Lecture)
11. Innate Immune Activation in Neovascular Age-related Macular Degeneration. Shenzhen International Sumit Frurm on Ophthalmology and Visual Science. July 2018, Shenzhen, China. (Invited speaker)
12. Inflammation in diabetic retinopathy. Molecular Mechanisms for Eye Development & Ocular Pathogenesis and Beyond Symposium. 8-9^th April 2018. Zhongshan Ophthalmic Center (ZOC) Guangzhou, China.  (Invited Speaker)
13. 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.  (Invited speaker)
14. The role of inflammation in diabetes-induced retinal microvascular degeneration. British Microcirculation Society Conference (Keynote). 16-17 April 2018. Nottingham, UK. (Key Note Speaker)
15. Taming inflammation for the management of retinal disease – what do we know, where do we go? Henan Eye Institute, 26-27^th November 2017, China. (Invited Lecture)
16. Metabolic control of microglial activation for the management of retinal degeneration. International Retinal Summit. 27-29 October 2017. Shenzhen, China. (Invited speaker)
17. Immune Privilege in the ageing eye. July 2017, Xiamen University, China. (Invited Lecture)
18. The role of STAT3 in diabetic retinopathy. The 9^th Chinese Congress of Research in Vision and Ophthalmology. April 2017, Beijing, China.  (Invited speaker)
19. Para-inflammation, chronic inflammation and age-related macular degeneration. ARVO Annual Meeting. May 2017, Baltimore, USA.  (Invited speaker and Modulator)
20. Metabolic control of microglial activation. ISER 2016 Biennial Meeting. Sept. 2016. Tokyo, Japan.  (Invited speaker and Modulator)
21.  Inflammation in age-related macular degeneration – what do we know about it? Sept. 2016. Zhongshan Ophthalmic Centre. Sun-Yat-Sen University. China.  (Invited speaker)
22. Molecular regulation of microglial activation in retinal degenerative disease. 5^th Global Chinese Ophthalmic Conference/21^st Congress of Chinese Ophthalmological Society. Sept. 2016, Suzhou, China.  (Invited speaker and Modulator)
23. Dysregulated para-inflammation and age-related macular degeneration. 9^th Internal Symposium on Uveitis. August 2016, Dublin, Ireland.  (Invited speaker)
24. Para-inflammation – what is it and why might it be important? 2016 ARVO Annual Meeting. Seattle, USA  (Invited speaker and Modulator)
25. Para-inflammation, the concept and its implications in age-related retinal diseases. Feb. 2016, University of Cologne, Germany. (Invited Lecture)
26. Para-inflammation, chronic inflammation and age-related macular degeneration. Danish Society of Immunology, November 2015, Copenhagen, Denmark.  (Invited speaker)
27. Deletion of SOCS3 in myeloid cells results in severe retinal inflammation and accelerated retinal angiogenesis in experimental autoimmune uveoretinitis. 5^th International Uveitis Symposium, Oct. 2015, Chongqing, China. (Invited speaker and Modulator)
28. Taming inflammation for the management of retinal degenerative diseases. Xiangya Hospital, Central South University of China. Oct. 2015. (Invited Lecture)
29. Immune cell activation in diabetic retinopathy. European Association for Vision and Eye Research (EVER) 2015 annual meeting. October 2015. Nice, France. (Invited speaker and Modulator)
30. Retinal innate immune activation in healthy and disease. European Association for Vision and Eye Research (EVER) 2015 annual meeting. October 2015. Nice, France. (Invited speaker and Modulator)
31. Innate immune response in neovascular age-related macular degeneration. 7^th Chinese Congress of Research in Vision and Ophthalmology. Aug. 2015. Shenyang, China.  (Invited speaker)
32. Regulation of retinal immune response in health and disease. Aug. 2015. Zhongshan Ophthalmic Center, China. (Invited Lecture)
33. Inflammation in diabetic retinopathy. May 2015. ThromboGenics NV. Leuven, Belgium.  (Invited speaker)
34. Systemic immune activation in age-related macular degeneration. May 2015. National Eye Institute (NEI), NIH, USA.  (Invited speaker)
35. Innate Immune Activation in age-related macular degeneration. March 2015. Cambridge Neuroscience Spring School. The University of Cambridge. UK. (Invited speaker)
36. Immunology of retinal degenerative disease. Association for Ocular Pharmacology & Therapeutics Annual Meeting. Feb 2015. Charleston, SC, USA.  (Invited speaker and Modulator)

• 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.