ReviewThe progress in understanding and treatment of diabetic retinopathy
Section snippets
The global significance of diabetic retinopathy
The global incidence of diabetes mellitus is set to rise dramatically from an estimated 382 million people in 2013 to 592 million by 2030 (Derakhshan et al., 2012, Guariguata et al., 2014, Rathmann and Giani, 2004). Type 1 diabetes (T1D) arises from an autoimmune destruction of beta cells in the endocrine pancreas causing severe insulin deficiency. Type 2 diabetes (T2D) is characterized by impaired insulin action (‘insulin resistance’) which is multifactorial in origin, and in its later stages,
Classification of diabetic retinopathy
Diabetes is thought to affect almost all of the 30 or more cell types in the retina. However, because the inner retinal vasculature is so readily visualized the classification and grading of retinopathy has been based on the severity of vascular lesions. The commonly used and now standard Early Treatment of Diabetic Retinopathy Study (ETDRS) scale (ETDRS, 1991) is based on the anatomical features of the retina and on the number of photographically detectable microvascular lesions. It must be
The importance of glucose
Normalisation of blood glucose levels is the ‘ideal’ in the management of people with diabetes, but actual targets for glycaemia must be tailored to the individual, taking into account risks of hypoglycaemia, especially in T1DM patients. In older patients, short-term risks of hypoglycaemia, risks associated with medications, and disruption of life must be carefully balanced against any longer-term benefits of tight control. The benefits of achieving ‘tight control’ early in the course of
Modelling diabetic retinopathy
As this review develops it will become clear that there is a need for further understanding of the molecular and cellular pathways involved in diabetic retinopathy and to utilise this knowledge for drug development. While patient based studies remain vital, there is also a requirement for models that facilitate experimental and hypothesis-driven research in this field. However, the inherent complexity and decades-long progression of diabetic retinopathy presents a serious challenge for
Features of retinal microvascular dysfunction during diabetes
As mentioned previously, the ETDRS clinical classification of diabetic retinopathy is based on vascular lesions since they are the most obvious in the fundus. As a result most research into the pathogenesis of diabetic retinopathy has concentrated on the microvasculopathy in the retina with a focus on how this leads to non-perfusion and hypoxia with resultant breakdown of the BRB, oedema and/or PDR. It is well established that retinal capillary pericytes and arteriolar smooth muscle cells are
Therapeutic options in diabetic retinopathy
At present there are few measures available to prevent diabetic retinopathy beyond regulating hyperglycaemia (DCCT, 1993), preventing dyslipidemia (Chowdhury et al., 2002), controlling hypertension (Kohner et al., 1995) and cessation of tobacco smoking (Schram et al., 2003). Patients who develop DMO can be treated with laser photocoagulation, intravitreal anti-VEGF drugs and intravitreal corticosteroids. For PDR, the standard interventions are laser photocoagulation and vitreoretinal surgery
Developing new therapies for diabetic retinopathy
The development of new therapies capable of preventing or slowing the onset and progression of diabetic retinopathy remains a priority. A wide range of new approaches based on retinal glial, neuronal and vascular pathophysiology during diabetes are being developed although, thus far, none have entered clinical use for early-stage diabetic retinopathy. Our ability to prevent initiation and progression of diabetic retinopathy is due to several factors: i) lack of understanding of what pathogenic
Summary
Diabetic retinopathy involves a highly complex interplay between biochemical and metabolic abnormalities occurring in almost all cells of the retina. Identification of a precise pathogenesis that links the neuroglial and microvascular damage occurring in the diabetic retina remains a valid goal. In the years to come, continued progress is anticipated as our understanding of the molecular and cellular basis of diabetic retinopathy improves in unison with patient-based research. We are also
Acknowledgements
The authors would like to acknowledge financial support from Fight for Sight (UK) (FFS 1316), The Sir Jules Thorn Trust (05SC/02A), The Medical Research Council (MRC) (MRC G0801962), The European Union (EC FP7 – Health 2012-305736), The British Heart Foundation (PG1/11/99/29027), British Heart Foundation, The Biotechnology and Biological Sciences Research Council (BBSRC) (BBSRC – BB/H005498/1), The Royal Society (WM100045), and the Juvenile Diabetes Research Foundation (JDRF-5-CDA-2014-225-A-N
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Percentage of work contributed by each author in the production of the manuscript is as follows: Stitt 20%; Curtis 10%; Chen 5%; Medina 5%; McKay 5%; Jenkins 5%, Gardiner 5%; Lyons 10%; Hammes 10%; Simo 10%; Lois 15%.