Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

<p>Abstract</p> <p>Background</p> <p>Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.</p> <p>Methods</p> <p>Ten patients with type 1 diabetes and ten healthy age- and weight-matched controls were studied. Aqueous flow was measured by fluorophotometry during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg/min). Intraocular pressure was measured by tonometry at -10, 90 and 240 minutes from the start of the clamp, and outflow facility was measured by tonography at 240 minutes.</p> <p>Results</p> <p>During conditions of identical glucose and insulin concentrations, mean aqueous flow was lower by 0.58 μl/min in the diabetes group compared to controls (2.58 ± 0.65 versus 3.16 ± 0.66 μl/min, respectively, mean ± SD, p = 0.07) but statistical significance was not reached. Before the clamp, IOP was higher in the diabetes group (22.6 ± 3.0 mm Hg) than in the control group (19.3 ± 1.8 mm Hg, p = 0.01) but at 90 minutes into the clamp, and for the remainder of the study, IOP was reduced in the diabetes group to the level of the control group. Ocular pulse amplitude and outflow facility were not different between groups. Systolic blood pressure was significantly higher in the diabetes group, but diastolic and mean arterial pressures were not different.</p> <p>Conclusions</p> <p>We conclude that compared to healthy participants, patients with type 1 diabetes having microalbuminuria and retinopathy have higher IOPs that are normalized by hyperinsulinemia. During the clamp, a reduction in aqueous flow was not statistically significant.</p

Ocular Delivery of Compacted DNA-Nanoparticles Does Not Elicit Toxicity in the Mouse Retina

Subretinal delivery of polyethylene glycol-substituted lysine peptide (CK30PEG)-compacted DNA nanoparticles results in efficient gene expression in retinal cells. This work evaluates the ocular safety of compacted DNA nanoparticles. CK30PEG-compacted nanoparticles containing an EGFP expression plasmid were subretinally injected in adult mice (1 µl at 0.3, 1.0 and 3.0 µg/µl). Retinas were examined for signs of inflammation at 1, 2, 4 and 7 days post-injection. Neither infiltration of polymorphonuclear neutrophils or lymphocytes was detected in retinas. In addition, elevation of macrophage marker F4/80 or myeloid marker myeloperoxidase was not detected in the injected eyes. The chemokine KC mRNA increased 3–4 fold in eyes injected with either nanoparticles or saline at 1 day post-injection, but returned to control levels at 2 days post-injection. No elevation of KC protein was observed in these mice. The monocyte chemotactic protein-1, increased 3–4 fold at 1 day post-injection for both nanoparticle and saline injected eyes, but also returned to control levels at 2 days. No elevations of tumor necrosis factor alpha mRNA or protein were detected. These investigations show no signs of local inflammatory responses associated with subretinal injection of compacted DNA nanoparticles, indicating that the retina may be a suitable target for clinical nanoparticle-based interventions

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease

Association Between Diabetes Mellitus And Glaucoma

It has not been determined definitively whether there is a significant association between diabetes mellitus (DM) and glaucoma. Some population-based studies have shown a positive association between diabetes and glaucoma, and others have shown negative association between diabetes and glaucoma. However in many studies that showed a lack of a significant association between diabetes and glaucoma, the diagnosis of DM was made by self-presentation. On the other hand, DM was diagnosed by the serum glucose level or by glucose tolerance tests in the Rotterdam Study. The study concluded that the risk of open angle glaucoma was increased by more than three times in patients with diabetes than without diabetes. The results of a recent metaanalysis suggested that diabetes was a significant risk factor for open angle glaucoma. However, two of 12 studies included in the meta-analysis used only high intraocular pressure (IOP) as a definition of open angle glaucoma. Thus, patients with normal tension glaucoma were not included in the glaucoma group. More exact definitions of DM and glaucoma should be used to determine more accurately the association between DM and glaucoma. The results of these studies indicate that there is insufficient clinical evidence to conclude that there is a significant relationship between diabetes mellitus and glaucoma

Flicker electroretinograms of eyes with cataract recorded with RETeval system before and after mydriasis

Gen Miura, Takayuki Baba, Toshiyuki Oshitari, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan Purpose: The aim of this study is to determine the effect of pupil size of eyes with cataracts on the flicker electroretinograms (ERGs) elicited and recorded with the RETeval system.Patients and methods: Forty-one eyes of 41 patients (mean age, 76.5&plusmn;7.3&nbsp;years) that had grade 2 nuclear or cortical cataract without any other abnormalities were studied. Flicker ERGs were recorded before and after mydriatic drops instillation. The ERGs were elicited by the white light delivered at the frequency of 28.3&nbsp;Hz and intensities of 2, 8, and 32 Td-s. The amplitudes and the implicit times of the flicker ERGs before and after mydriasis were compared.Results: There were no significant differences between the amplitudes before and after mydriasis (P=0.35, 2 Td-s; P=0.31, 8 Td-s; P=0.50, 32 Td-s). There were also no significant differences between the implicit times before and after mydriasis (P=0.86, 2 Td-s; P=0.98, 8 Td-s; P=0.95, 32 Td-s). The mean amplitudes and implicit times of the nuclear and cortical cataracts groups before the mydriasis were also not significantly different from those after mydriasis for all stimulus intensities.Conclusion: The lack of significant differences in the amplitudes and the implicit times of the flicker ERG of cataractous eyes before and after mydriasis indicated that the RETeval flicker ERGs in cataractous eyes is less affected by the pupil diameter. With our earlier study, it was assumed that the effect of cataracts on the RETeval flicker ERGs was due to the opacity of the crystalline lens, and the influence of the cataract would not be reduced or increased by mydriasis. Keywords: electroretinogram, ERG, flicker ERG, cataract, RETeva