Maternal immune system adaptation to pregnancy - a potential influence on the course of diabetic retinopathy

Abstract

BackgroundProgression of diabetic retinopathy occurs at least temporarily during pregnancy. Although the cause of this progression is not entirely understood, the immune phenomenon and chronic inflammation may play a significant role. During pregnancy in order to avoid fetus rejection, certain components of the immune system that are knowingly implicated in the pathogenesis of diabetic retinopathy are activated including generalized leukocyte activation and an increase in certain cytokine plasma levels. Activated leukocytes with up regulated adhesion molecules have an increased potential to bind to the endothelium cells of blood vessels. Leukocyte-endothelial interaction and the consequent leukostasis with capillary occlusion, ischemia and vascular leakage have a substantial role in the development of diabetic retinopathy. Furthermore, certain increased cytokines are known to cause blood-retinal-barrier breakdown whilst others promote angiogenic and fibrovascular proliferation and thereby can also be implicated in the pathogenesis of this diabetic complication.Presentation of the hypothesisWe hypothesized that the activation of the immune system during gestation may have an influence on the course of retinopathy in pregnant diabetic women.Testing the hypothesisWe suggest two prospective follow up studies conducted on women with type 1 diabetes mellitus. The first study would include a group of non-pregnant women and a group of diabetic women undergoing normal pregnancy matched for age and duration of diabetes. In the second study pregnant women would be divided into two groups: one with normal pregnancy and the other with preeclampsia. The procedure and data collection in both studies will be identical: a complete ophthalmological examination, glycaemic control, blood pressure measurement and venous blood samples for the determination of plasma levels of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8) and adhesion molecules (ICAM-1, VCAM-1).Implications of the hypothesisConsidering the present assumption, the gestational immune activation could be suggested as a potential risk factor for the development and progression of retinopathy in diabetic women. A better understanding of immunomodulatory effects of pregnancy on diabetic retinopathy pave the way for further investigations of the mechanism of its pathogenesis and could be essential for novel approaches to the treatment of this serious sight threatening complication of diabetes mellitus.

Identification of VEGF-Independent Cytokines in Proliferative Diabetic Retinopathy Vitreous

“…The remaining 14 cytokines including eotaxin, FGF-2, MIP-1b, VEGF, FLT-3L, GRO, interleukins 1a, 6, 7, 8, and 10, IP-10, MCP-1, and MDC were previously observed to be elevated in vitreous of patients with PDR. [11][12][13][14][15][16][17][18][19][20] Similar results were obtained by Mann-Whitney analysis ( Supplementary Table S2, left column), except that Mann-Whitney analysis identified two additional cytokines, G-CSF and sIL-2ra, as significantly elevated in PDR patient vitreous ( Supplementary Table S2, right column). Cytokine levels were markedly different between patient samples.…”

Ocular changes during pregnancy

“…It is found that some immune system components that have a known association with pathogenesis of diabetic retinopathy are activated during pregnancy. 53 , 54 …”

Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss

“…At the end of 6.5 years of follow-up on average, prevalence and severity of retinopathy was comparable between women with pregnancies and women without pregnancies [ 83 ]. Possible mechanisms behind the progression of DR in pregnancy include both hormonal and immune theories [ 84 , 85 ].…”