Anna Polosa

Choroidal Involution Is Associated with a Progressive Degeneration of the Outer Retinal Function in a Model of Retinopathy of Prematurity: Early Role for IL-1β

Retinopathy of prematurity (ROP), the most common cause of blindness in premature infants, has long been associated with inner retinal alterations. However, recent studies reveal outer retinal dysfunctions in patients formerly afflicted with ROP. We have recently demonstrated that choroidal involution occurs early in retinopathy. Herein, we investigated the mechanisms underlying the choroidal involution and its long-term impact on retinal function. An oxygen-induced retinopathy (OIR) model was used. Inxa0vitro and exxa0vivo assays were applied to evaluate cytotoxic effects of IL-1β on choroidal endothelium. Electroretinogram was used to evaluate visual function. We found that proinflammatory IL-1β was markedly increased in retinal pigment epithelium (RPE)/choroid and positively correlated with choroidal degeneration in the early stages of retinopathy. IL-1β was found to be cytotoxic to choroid inxa0vitro, exxa0vivo, and inxa0vivo. Long-term effects on choroidal involution included a hypoxic outer neuroretina, associated with a progressive loss of RPE and photoreceptors, and visual deterioration. Early inhibition of IL-1β receptor preserved choroid, decreased subretinal hypoxia, and prevented RPE/photoreceptor death, resulting in life-long improved visual function in IL-1 receptor antagonist-treated OIR animals. Together, these findings suggest a critical role for IL-1β-induced choroidal degeneration in outer retinal dysfunction. Neonatal therapy using IL-1 receptor antagonist preserves choroid and prevents protracted outer neuroretinal anomalies in OIR, suggesting IL-1β as a potential therapeutic target in ROP.

Strain Differences in Light-Induced Retinopathy.

The purpose of this study was to better understand the role of ocular pigmentation and genetics in light-induced retinal damage. Adult pigmented [Long Evans (LE) and Brown Norway (BN)] and albino [Sprague Dawley (SD) and Lewis (LW)] rats were exposed to a bright cyclic light for 6 consecutive days and where compared with juvenile animals exposed to the same bright light environment from postnatal age 14 to 28. Flash ERGs and retinal histology were performed at predetermined days (D) post-light exposure. At D1, ERGs were similar in all adult groups with no recordable a-waves and residual b-waves. A transient recovery was noticed at D30 in the LW and LE only [b-wave: 18% and 25% of their original amplitude respectively]. Histology revealed that BN retina was the most damaged, while LE retina was best preserved. SD and LW rats were almost as damaged as BN rats. In contrast, the retina of juvenile BN was almost as resistant to the bright light exposure as that of juvenile LE rats. Our results strongly suggest that, although ocular pigmentation and genetic background are important factors in regulating the severity of light-induced retinal damage, the age of the animal at the onset of light exposure appears to be the most important determining factor.

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.

Characterizing the Retinal Function of Psammomys obesus: A Diurnal Rodent Model to Study Human Retinal Function

ABSTRACT Purpose: To compare the retinal function of a diurnal murid rodent, Psammomys obesus, with that of Wistar albino rat and human subjects. Materials and methods: Adult Psammomys obesus were captured and transferred to the animal facilities where they were maintained at 25°C with standard light/dark cycles and natural halophilic plants, rich in water and mineral salts. Standard full-field photopic and scotopic electroretinograms were obtained. Results: The right eye of all animals displayed well detectable and reproducible scotopic and photopic electroretinogram (ERG) responses. Results were compared with those obtained from human subjects and Wistar rats. ERG measurement showed that the amplitudes of scotopic responses in Psammomys obesus are quite similar to those of human subjects. The amplitude of the photopic a-wave was comparable to that of humans and six times higher than that of the albino rat. The amplitudes of photopic b-wave, photopic oscillatory potentials (OPs), and 30 Hz flicker were all markedly larger in Psammomys obesus compared to those obtained from human subjects and Wistar rats. Furthermore, like the human photopic ERG, the photopic ERG of Psammomys obesus also includes prominent post b-wave components (i.e. i- and d-waves) while the ERG of Wistar rats does not. Conclusions: Our results suggest that the retinal function of Psammomys obesus, especially the cone-mediated function, shares several features with that of human subjects. We believe that Psammomys obesus represents an interesting alternative to study the structure and function of the normal and diseased retina in a human-like rodent model of retinal function.

Light-Induced Retinopathy: Young Age Protects more than Ocular Pigmentation

ABSTRACT Purpose: The purpose of this study was to compare the efficacy that ocular melanin confers in protecting the retina of juvenile and adult rats exposed to a bright luminous environment. Methods: Juvenile (JLE) and adult (ALE) Long–Evans pigmented rats were thus exposed to a bright cyclic light (10,000lux; white light) from postnatal day 14–28 or for 6 consecutive days, respectively. Flash electroretinograms (ERG) and retinal histology were performed at different predetermined ages, post-light exposure. Results: Despite a significant reduction in ERG responses immediately following light exposure, with time, retinal function fully recovered in JLE compared to a 54% recovery for the ALE. In ALE, we noted a region of the supero-temporal quadrant that was highly vulnerable to light damage. This region was also devoid of melanin granules prior to the light exposure. This melanin-free zone increased in size in the days that followed the end of exposure, a process that was accompanied by the gradual degeneration of the thus uncovered photoreceptors. In contrast, melanin and photoreceptor losses were minimal in JLE. Conclusion: Our results suggest that the light-induced photoreceptor degeneration in ALE would be secondary to the initial destruction of the RPE and ensuing loss of melanin protection. In contrast, the melanin granules of JLE appear to be significantly more resistant to light damage, a characteristic that would explain the higher resistance of JLE photoreceptors to light damage. Our results would thus suggest that the efficacy of ocular melanin protection against light damage declines with age.