Colin J Chu

University of Bristol | UB · School of Clinical Sciences

Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition recept...

Purpose To compare the visual outcome and the rate of intraoperative complications in eyes of diabetic and non-diabetic patients undergoing phacoemulsification over 15 years Design Retrospective clinical cohort study Methods Data of 179,159 eyes that underwent phacoemulsification at 8 centers were classified based on the presence or absence of di...

Our recent work characterized the movement of single blood cells within the retinal vasculature (Joseph et al. 2019) using adaptive optics ophthalmoscopy. Here, we apply this technique to the context of acute inflammation and discover both infiltrating and tissue-resident immune cells to be visible without any labeling in the living mouse retina us...

Our recent work characterized the movement of single blood cells within the retinal vasculature (Joseph et al. 2019) using adaptive optics ophthalmoscopy. Here, we apply this technique to the context of acute inflammation and discover both infiltrating and tissue-resident immune cells to be visible without any labeling in the living mouse retina us...

Our recent work characterized the movement of single blood cells within the retinal vasculature (Joseph et al. 2019) using adaptive optics ophthalmoscopy. Here, we apply this technique to the context of acute inflammation and discover both infiltrating and tissue-resident immune cells to be visible without any labeling in the living mouse retina us...

Our recent work characterized the movement of single blood cells within the retinal vasculature of healthy mice (Joseph et al. 2019) using adaptive optics ophthalmoscopy. Here we apply this technique to the context of acute inflammation and discover both infiltrating and tissue-resident immune cells to be visible without any labelling in the living...

PRéCIS:: A large cohort undergoing cataract extraction was retrospectively analyzed to ascertain the degree of real-world IOP reduction in normal eyes and those with glaucoma and a predictive formula was developed. Purpose: To define the real-world degree of intraocular pressure (IOP) reduction following cataract extraction to guide its role as a...

The eye is ideally suited for unperturbed longitudinal intravital imaging of immune responses. No confounding inflammatory surgery, externalization or depressurization is required for access as it is uniquely transparent. Directly imaging immune cells in vivo would greatly advance our biological understanding but it is not currently possible in man...

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells withi...

Glaucoma is a common cause of blindness, yet current therapeutic options are imperfect. Clinical trials have invariably shown that reduction in intraocular pressure (IOP) regardless of disease subtype prevents visual loss. Reducing ciliary body aqueous humor production can lower IOP, and the adeno-associated virus ShH10 serotype was identified as a...

Background: Whether retinal microglia can maintain or restore immune homeostasis during and after inflammation is unclear. We performed single-eye mRNA-sequencing on microglia at different timepoints following a single inflammatory stimulus to characterise their transcriptome during and after resolution of endotoxin-induced uveitis (EIU). Experimen...

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells withi...

Aims: To evaluate retinal vasculature changes in primary open angle glaucoma (POAG) and whether the functional visual loss correlates with parameters obtained using optical coherence tomography angiography (OCTA). Materials and Methods: OCT and OCTA images were collected from 116 POAG eyes and 40 normal eyes in a prospective, cross-sectional observ...

Purpose: To analyze the visual outcomes and rate of intraoperative complications of phacoemulsification surgery after prior pars plana vitrectomy (PPV). Design: Retrospective, multicenter database study. Participants: Eyes that underwent phacoemulsification between June 2005 and March 2015 at 8 sites in the United Kingdom. Methods: Study eye...

Importance Primary epiretinal membrane (ERM) is a common retinal disorder with a prevalence of 4% to 18.5%. Although ERM and cataracts commonly occur together, to our knowledge, no studies have investigated the outcome of cataract surgery alone in this setting. Objective To analyze the visual outcome and cystoid macular edema risk with cataract su...

PurposeThe aim of this study was to determine a sequence of structural changes in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography-angiography (OCT-A) and comparing with other imaging modalities.Patients and methodsPatients with a new diagnosis of acute-onset APMPPE referred to a regional special...

Background/aims: Cataract is an important source of visual loss in patients with uveitis. Whether or not outcomes of cataract surgery in eyes with uveitis are worse compared with non-uveitic eyes have to date been compromised by lack of reliable estimates of benefit and harm, which require data from large cohorts. Methods: Electronic medical rec...

Endotoxin-induced uveitis (EIU) is a model of acute TLR4-mediated organ inflammation, which has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific cell count scoring with histological sections upon each ey...

Purpose To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. Design Retrospective database study of electronic medical records (EMRs). Participants A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom cli...

We have developed a method to label and image myeloid cells infiltrating the mouse retina and choroid in vivo, using a single depot injection of Indocyanine green dye (ICG). This was demonstrated using different ocular models of inflammation and angiogenesis - endotoxin-induced uveitis (EIU), experimental autoimmune uveoretinitis (EAU) and laser-in...

Elevated tumor necrosis factor (TNF) α levels are associated with chronic autoimmune diseases in which effects of TNFα on immune cells are multiple and complex. Analysis of uveitis in mice exhibiting severe autoimmune inflammation, resulting in a destructive subtotal loss of photoreceptors, revealed the presence of high plasma levels of TNFα and a...

To investigate the relationships between peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography (FA). Cross-sectional, consecutive case series. Consecutive ultra-widefield FA images were collected from 82 uveitis patients (82 eyes) in a single center. The extent of peripheral vasculitis, capil...

Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecule and while described as a repressor of innate immune responses, the role of Anx-A1 in adaptive immunity, and in particular in T helper (Th) cell responses, remains controversial. We have used a T-cell mediated mouse model of retinal autoimmune disease to unravel the role of Anx-A1 in th...

Understanding phenotype–genotype correlations in retinal degeneration is a major challenge. Mutations in CRB1 lead to a spectrum of autosomal recessive retinal dystrophies with variable phenotypes suggesting the influence of modifying factors. To establish the contribution of the genetic background to phenotypic variability associated with the Crb1...

Experimental autoimmune uveoretinitis is a model for noninfectious posterior segment intraocular inflammation in humans. Although this disease is CD4(+) T cell dependent, in the persistent phase of disease CD8(+) T cells accumulate. We show that these are effector memory CD8(+) T cells that differ from their splenic counterparts with respect to sur...

Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice. Considerable progress has been made in differentiating embryonic stem cell...

Despite advances in clinical imaging and grading our understanding of retinal immune responses and their morphological correlates in experimental autoimmune uveoretinitis (EAU), has been hindered by the requirement for post-mortem histology. To date, monitoring changes occurring during EAU disease progression and evaluating the effect of therapeuti...

OCT based EAU scoring scan acquisition. A summary of the imaging series for scoring, using an example composition. For each eye, eight combined IR+OCT scans are acquired (A–H). Simultaneous FFA can be performed where required. The 30-degree field of view is centred on the optic nerve head. A) Horizontal scan through the disc. B) Horizontal scan, 30...

A worked example of the scoring system using the image acquisition described in Figure S1. Using all eight scans, each eye is scored across four domains and the raw results displayed. The number of discrete vitreous opacities, separated from the retina are counted in the scan that shows the strongest effect (A). Clusters that would receive scores a...

The appearance and correlation with retinal anatomy obtained by OCT scanning. An OCT scan from a non-induced C57BL/6 mouse is displayed next to a matched histological section stained with haematoxylin and eosin. (TIF)

3D reconstruction of retinal folds in an eye 80 days post-induction of EAU. (AVI)

OCT can track the development of tissue changes over time. Each column illustrates the development of a feature from the identical eye of an animal at the same manually located region on OCT for the four main features. Due to the intrinsic variability of the model, the timing and severity of changes varies between animals, but a general trend to ea...

3D reconstruction of an intraretinal vascular abnormality in an eye 36 days post-induction of EAU. (AVI)

Noninfectious intraocular inflammatory disease remains a significant cause of visual loss, even with current systemic immunosuppression. Alternative novel treatments are thus required, particularly for severe forms of posterior uveitis. Encouraging results from several phase I/II clinical trials of gene therapy for monogenic retinal disorders have...

Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening. METHODS AND OUTCOMES: We conducted a systematic...

Asymptomatic bilateral optic disc swelling was detected in a 19-year-old man with type 1 diabetes through routine photographic screening for retinopathy. He was found to have significant vitamin B(12) deficiency which the authors believe was the cause for the optic neuropathy. After B(12) replacement, visual function and optic disc appearances retu...

Horner’s syndrome describes a triad of pupillary miosis, partial eyelid ptosis and facial anhidrosis caused by disruption of the sympathetic pathway from the posterior hypothalamus to the eye. Diagnostic confirmation is crucial as causes can include lifethreatening carotid dissection and apical lung tumours. Often the signs are subtle, with a diffe...