Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy.

There is a significant genetic component associated with the risk of developing age-related macular degeneration (AMD), a leading cause of blindness among older people in Western countries. Based on the recognized role of CX3CR1, a chemokine receptor, in other age-related complex diseases and the possible involvement of the immune system in AMD pathogenesis, we tested for an association between CX3CR1 sequence variation/expression and AMD by screening two CX3CR1 single nucleotide polymorphisms (SNPs), V249I and T280M, among AMD patients and controls, and determining the level of CX3CR1 expression in AMD and normal eye tissues. PRINCIPAL FINDINGS1. An association between CX3CR1 1249/M280 alleles and AMD A significant increased prevalence of M280 and 1249 carriers or alleles was found among AMD cases vs. controls. Distribution of CX3CR1V249I and T280M did not deviate from Hardy-Weinberg equilibrium in any group (Table 1). A quantitative correlation between CX3CR1 1249/M280 and the prevalence of AMD phenotypeAs indicated in Table 1, the odds ratios (OR) of clinically diagnosed AMD compared with controls were 1.86 and 1.94 in terms of carrying 1249 and M280, respectively; however, the OR of pathologically diagnosed AMD reached 3.57 in terms of carrying M280. A higher OR was found for the clinically diagnosed AMD group compared with the aged controls whereas a lower OR was observed for the AMD group compared with the blood donor population of a much younger age. Allele frequency analysis yielded similar results (see full text version).3. Lower expression of CX3CR1 in the AMD maculae from individual bearing CX3CR1 T/M280 compared with individual bearing CX3CR1 T/T280

OBJECTIVE—Diabetes is a leading cause of morbidity and mortality. The purpose of this study is to assess the associations between diabetes complications and mortality in the Early Treatment Diabetic Retinopathy Study (ETDRS). RESEARCH DESIGN AND METHODS—We examined demographic, clinical, and laboratory characteristics of the 3,711 subjects enrolled in the ETDRS, a randomized controlled clinical trial designed to evaluate the role of laser photocoagulation and aspirin therapy for diabetic retinopathy. The outcome assessed was all-cause mortality. Multivariable Cox proportional hazards regression was used to assess associations between diabetes complications and mortality for type 1 and type 2 diabetes separately. RESULTS—The 5-year estimates of all-cause mortality were 5.5 and 18.9% for patients with type 1 and type 2 diabetes, respectively. In patients with type 1 diabetes, amputation (hazard ratio [HR] 5.08 [95% CI 2.06–12.54]) and poor visual acuity (1.74 [1.10–2.75]) remained significantly associated with mortality, after adjusting for other diabetes complications and baseline characteristics. In patients with type 2 diabetes, macrovascular disease and worsening levels of nephropathy, neuropathy, retinopathy, and visual acuity are associated with progressively increasing risks of mortality, after controlling for other baseline risk factors. CONCLUSIONS—Amputation is the strongest predictor for mortality in patients with type 1 diabetes. All complications independently predict mortality in patients with type 2 diabetes. There is an increased risk for mortality as the degree of each complication worsens. Additional studies are needed to investigate the effectiveness of tertiary prevention to decrease mortality in these patients.