Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, Trav. 14, 101, São Paulo, SP 05508-090, Brasil.
College of Public Health, University of South Florida, Tampa, FL 33612, USA.
Integr Comp Biol. 2024 Nov 21;64(5):1309-1319. doi: 10.1093/icb/icae026.
Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in amphibians, little information is available about the natural variation in ocular melatonin levels and its modulation following immune stimulation. We investigated the daily variation of plasma and ocular melatonin levels in bullfrogs (Lithobates catesbeianus) and their modulation following an immune stimulation with lipopolysaccharide (LPS) in yellow cururu toads (Rhinella icterica). For the daily variation, bullfrogs were bled and then euthanized for eye collection every 3 h over 24 h to determine plasma and ocular melatonin levels. We found a positive correlation between ocular and plasma melatonin levels, with maximum values at night (22 h) for both plasma and the eyes. For immune stimulation, yellow cururu toads received an intraperitoneal injection of LPS or saline solution during the day (10 h) or at night (22 h). Two hours after injection, toads were bled and euthanized for eye collection to obtain plasma and ocular melatonin levels. In addition, the liver and bone marrow were collected to investigate local melatonin modulation. Our results demonstrate that retinal light-controlled rhythmic melatonin production is suppressed while liver and bone marrow melatonin levels increase during the inflammatory assemblage in anurans. Interestingly, the LPS injection decreased only ocular melatonin levels, reinforcing the central role of the eyes (i.e., retina) as an essential organ of melatonin production, and a similar role to the pineal gland during the inflammatory response in amphibians. Together, these results point to a possible immune-pineal-ocular axis in amphibians, yet to be fully described in this group.
褪黑素是一种已知的激素，作为白天黑暗阶段的内源性时间标记物。尽管眼睛似乎是两栖动物褪黑素产生的主要部位，但关于眼部褪黑素水平的自然变化及其在免疫刺激后的调节知之甚少。我们研究了牛蛙（Lithobates catesbeianus）血浆和眼部褪黑素水平的日变化及其在黄cururu 蟾蜍（Rhinella icterica）中用脂多糖（LPS）免疫刺激后的调节。对于每日变化，牛蛙每隔 3 小时采血一次，然后在 24 小时内每 3 小时处死一次以收集眼部褪黑素水平。我们发现眼部和血浆褪黑素水平之间存在正相关，血浆和眼部的最大值均在夜间（22 小时）。对于免疫刺激，黄cururu 蟾蜍在白天（10 小时）或夜间（22 小时）接受 LPS 或生理盐水的腹腔内注射。注射后 2 小时，蟾蜍采血并处死以收集眼部褪黑素水平。此外，还收集了肝脏和骨髓以研究局部褪黑素的调节。我们的结果表明，在两栖动物的炎症聚集过程中，视网膜光控节律性褪黑素产生受到抑制，而肝脏和骨髓褪黑素水平增加。有趣的是，LPS 注射仅降低了眼部褪黑素水平，这加强了眼睛（即视网膜）作为褪黑素产生的重要器官的中心作用，以及在两栖动物炎症反应中与松果体相似的作用。总之，这些结果表明在两栖动物中存在一个可能的免疫-松果体-眼睛轴，但在该组中尚未完全描述。
