Evaluating the neuroprotective effect of 17ß-estradiol in rodent models of oxidative retinopathies.

PURPOSE: To determine the neuroprotective effect of estrogen on the structure and function of the retina exposed to an oxidative stress. METHODS: Male Sprague-Dawley rat pups were exposed to either hyperoxia (O2E: from P8 to P14) or bright light (LE: from P14 to P28) with or without 17 ß-estradiol (ßE2) treatment. Retinal structure (histology) and function (ERG) were assessed at selected time points. RESULTS: In the O2E model, ßE2 injections caused a significant reduction of the ERG and a significantly thinner OPL compared to untreated oxygen-exposed group (O2-exposed) rats. In contrast, in the LE model ßE2, treatment was beneficial to the retinal structure (thicker ONL) and function (better preserved ERG amplitudes) compared to untreated light-exposed group (light-exposed rats). CONCLUSION: Our results show that in conditions where the primary target of the oxidative stress is the outer retina (i.e., the photoreceptors) estrogen can protect the retina, while in situations where the inner retina (or retinal vasculature) is the main site of oxidative damage, estrogen may potentiate the detrimental effect of oxidative stress on the retina.

Sex and gender differences in mild traumatic brain injury/concussion.

The high incidence of concussions/mild traumatic brain injury and the significant number of people with persisting concussion symptoms as well as the concern for delayed, neurodegenerative effects of concussions makes them a major public health concern. There is much to learn on concussions with respect to pathophysiology as well as vulnerability and resiliency factors. The heterogeneity in outcome after a concussion warrants a more personalized approach to better understand the biological and psychosocial factors that may affect outcome. In this chapter we address biological sex and gender as they impact different aspects of concussion including incidence, risk factors and outcome. As well, this chapter will provide a more fulsome overview of intimate partner violence, an often-overlooked cause of concussion in women. Applying the sex and gender lens to concussion/mild traumatic brain injury is imperative for discovery of its pathophysiology and moving closer to treatments.

Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle.

PURPOSE: Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. METHOD: The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5-6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. RESULTS: Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. CONCLUSION: Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function.

Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function.

PURPOSE: Perinatal inflammatory stress in preterm babies is associated with increased rates of severe retinopathy of prematurity (ROP) and adverse neurological dysfunction. In this study, we set out to determine the consequences of severe systemic inflammatory stress on developmental retinal vascularization and evaluate the subsequent outcome on retinal function in later life. METHODS: Systemic inflammatory stress was induced in C57BL/6J mouse pups by an intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg) at postnatal day 4. In response to LPS, retinal inflammation was confirmed by quantitative RT-PCR analysis of diverse inflammatory markers. A detailed and systematic analysis of retinal microglial infiltration, retinal vascular morphology, density, and growth rate was performed at key time points throughout retinal vascularization. Retinal function in adult life was assessed by using electroretinography at 6 weeks postinjection. RESULTS: As early as 48 hours after intraperitoneal administration of LPS, a significant increase in retinal vascular density was noted throughout the retina. A pronounced increase in the number of activated microglial cell was observed in the retinal ganglion cell layer and in the outer plexiform layer just prior to their vascularization; direct physical contact between activated microglia and sprouting vessels suggested that microglia partake in promoting the aberrant retinal vascularization. With maturity, animals subjected to perinatal inflammatory stress displayed depleted retinal vascular beds and had significantly decreased retinal function as determined by electroretinography. CONCLUSIONS: Our data reveal that early severe postnatal inflammatory stress leads to abnormal retinal vascular development and increased vessel anastomosis and, ultimately, permanently compromises retinal function. The aberrant and initially exaggerated retinal vascularization observed is associated with microglial activation, providing a cellular mechanism by which perinatal sepsis predisposes to ROP.