RESUMO
Vision disorders are one of the most serious complications of diabetes mellitus (DM) affecting the quality of life of patients and eventually cause blindness. The ocular lesions in diabetes mellitus are located mainly in the blood vessels and retina layers. Different retina lesions could be grouped under the umbrella term of diabetic retinopathies (DMRP).We propose that one of the main causes in the etiopathogenesis of the DMRP consists of a progressive loss of the selective permeability of blood retinal barriers (BRB). The loss of selective permeability of blood retinal barriers will cause a progressive autoimmune process. Prolonged autoimmune injures in the retinal territory will triggers and maintains a low-grade chronic inflammation process, microvascular alterations, glial proliferation and subsequent fibrosis and worse, progressive apoptosis of the photoreceptor neurons.Patients with long-standing DM disturbances in retinal BRBs suffer of alterations in the enzymatic pathways of polyunsaturated fatty acids (PUFAs), increase release of free radicals and pro-inflammatory molecules and subsequently incremented levels of vascular endothelial growth factor. These facts can produce retinal edema and photoreceptor apoptosis.Experimental, clinical and epidemiological evidences showing that adequate metabolic and alimentary controls and constant practices of healthy life may avoid, retard or make less severe the appearance of DMRP. Considering the high demand for PUFAs ω3 by photoreceptor complexes of the retina, it seems advisable to take fish oil supplements (2 g per day). The cellular, subcellular and molecular basis of the propositions exposed above is developed in this article.Synthesizer drawings the most relevant findings of the ultrastructural pathology, as well as the main metabolic pathways of the PUFAs involved in balance and disbalanced conditions are provided.
Assuntos
Autoimunidade , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/patologia , Retinopatia Diabética/imunologia , Retinopatia Diabética/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Inflamação/patologia , Animais , Retinopatia Diabética/patologia , Diretrizes para o Planejamento em Saúde , HumanosRESUMO
PURPOSE: To evaluate the effects of benzalkonium chloride (BAK) on the blood-aqueous (BAB) and blood-retinal barriers (BRB) of pseudophakic eyes. METHODS: Prospective, randomized, investigator-masked, comparative study. Patients were randomly assigned to preservative-free artificial tears or BAK-preserved artificial tears. One drop of artificial tears was instilled 4 times a day in the study eye, starting the day after randomization for 30 days. Anterior chamber flare was assessed by a laser flare meter (LFM) and macular thickness measurements were obtained with optical coherence tomography, before, 15, and 30 days after randomization. RESULTS: A total of 44 healthy eyes of 44 pseudophakic volunteers were recruited. There were no significant differences regarding demographics (age, gender, and race distributions) and clinical characteristics (eye, mean intraocular pressure, and mean best-corrected visual acuity) between the 2 groups (P>0.05). No significant differences in baseline mean LFM values were observed (P=0.262). However, we detected a statistically significant increase in mean LFM measurements in the BAK-preserved group (11.4 ± 5.1 ph/ms) (P=0.017) after 15 days. After 30 days, the BAK-preserved group maintained significantly higher flare values (11.9 ± 5.9 ph/ms) compared with baseline (P=0.043). On the other hand, the preservative-free group showed mean flare values of 8.4 ± 2.5 ph/ms, not significantly different from those obtained at baseline (P=1.00). We observed no statistically significant change in macular thickness measurements at days 15 and 30 in either group (P>0.05). Cystoid macular edema was not detected in this series. CONCLUSIONS: Our results suggest that a short-term exposure to BAK can cause disruption of the BAB, without altering the BRB in pseudophakic eyes.
Assuntos
Compostos de Benzalcônio/administração & dosagem , Barreira Hematoaquosa/efeitos dos fármacos , Barreira Hematorretiniana/efeitos dos fármacos , Lubrificantes Oftálmicos/administração & dosagem , Conservantes Farmacêuticos/administração & dosagem , Pseudofacia/tratamento farmacológico , Idoso , Compostos de Benzalcônio/efeitos adversos , Barreira Hematoaquosa/patologia , Barreira Hematorretiniana/patologia , Feminino , Humanos , Lubrificantes Oftálmicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Estudos Prospectivos , Pseudofacia/diagnóstico , Método Simples-Cego , Resultado do TratamentoRESUMO
Diabetic retinopathy is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes. Diabetes was induced by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 minutes; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, whereas the contralateral eye was submitted to a sham procedure. Diabetic retinopathy was evaluated in terms of i) retinal function (electroretinogram and oscillatory potentials), ii) integrity of blood-retinal barrier (by albumin-Evans blue complex leakage and astrocyte glial fibrillary acidic protein IHC), iii) optical and electron microscopy histopathologic studies, and iv) vascular endothelial growth factor levels (using Western blot analysis and IHC). Brief ischemia pulses significantly preserved electroretinogram a- and b-wave and oscillatory potentials, avoided albumin-Evans blue leakage, prevented the decrease in astrocyte glial fibrillary acidic protein levels, reduced the appearance of retinal edemas, and prevented the increase in vascular endothelial growth factor levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies for diabetic retinopathy treatment.