Date Published: July 13, 2017
Publisher: Public Library of Science
Author(s): Yuko Nishikawa, Seita Morishita, Taeko Horie, Masanori Fukumoto, Takaki Sato, Teruyo Kida, Hidehiro Oku, Jun Sugasawa, Tsunehiko Ikeda, Kimitoshi Nakamura, Sanjoy Bhattacharya.
The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases. No statistically significant age differences existed among the groups. Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM: 6.67±4.04/18.82±7.10, MH: 10.3±7.02/17.00±4.8, PDR: 4.2±3.05/15.83±3.46, and RD: 10.00±4.58/16.06±4.57, while those in serum were ERM: 31.67±5.51/5.82±1.08, MH: 21.00±8.89/7.53±3.2, PDR: 29.20±7.07/12.75±10.62, and RD: 24.33±6.51/7.5±4.42. E2 concentrations were significantly higher (P<0.001) in the male serum than vitreous, yet significantly higher in the female vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female vitreous were ERM: 0.15±0.03/0.15±0.01, MH: 0.15±0.01/0.15±0.01, PDR: 0.15±0.03/0.16±0.12, and RD: 0.14±0.01/0.17±0.08, while those in serum were ERM: 4.54±1.46/0.16±0.01, MH: 8.04±2.29/0.16±0.10, PDR: 5.14±1.54/0.22±0.11, and RD: 3.24±0.75/0.17±0.10. T concentrations were high in the male serum, yet extremely low in the male and female vitreous and female serum. High concentrations of E2 were found in the vitreous, and women, in particular, exhibited significantly higher concentrations in the vitreous than in the serum. This finding suggests the possibility that in vitreoretinal disease cases, the synthesis of E2 is increased locally only in female eyes.
The brain has traditionally been perceived as the target organ of steroid hormones synthesized by the peripheral endocrine organs, such as the adrenal glands and reproductive organs. However, Baulieu et al  and Tsutsui et al [2,3] reported that the brain also produces steroid hormones on its own. An enzyme (P450scc) that synthesizes cholesterol to pregnenolone (P5) in the retina is present in retinal ganglion cells (RGCs) and is reportedly involved in the production of neurosteroids . It has also been reported that estrogen and androgen affect retinal thickness, raising the possibility that sex steroids play an important role in the retina [4,5].
In this study, the following four vitreoretinal diseases were examined: idiopathic epiretinal membrane (ERM), idiopathic macular hole (MH), proliferative diabetic retinopathy (PDR), and rhegmatogenous retinal detachment (RD). Measurements of E2 were taken in a total of 71 patients seen at the Department of Ophthalmology, Osaka Medical College Hospital, Takatsuki City, Japan from April 2013 through August 2016: 14 ERM patients (3 males and 11 females), 18 MH patients (3 males and 15 females), 20 PDR patients (10 males and 10 females), and 19 RD patients (3 males and 16 females). Measurements of T were taken in a total of 61 patients seen at the Department of Ophthalmology, Osaka Medical College Hospital from April 2013 through August 2016: 14 ERM patients (12 males and 2 females), 17 MH patients (2 males and 15 females), 13 PDR patients (9 males and 4 females), and 17 RD patients (6 males and 11 females). Since sample volumes were insufficient, we were unable to measure both E2 and T in each patient. The mean age (± standard deviation) of the male and female E2-measurement patients was 61.9 ± 14.8 years (range: 53–76 years) and 67.4 ± 6.7 years (range: 56–86 years), respectively, while that of the male and female T-measurement patients was 58.6 ± 15.5 years (range: 48–71 years) and 64.5 ± 10.6 years (range: 52–79 years), respectively. There was no statistically significant age difference among the groups. All operations were performed at Osaka Medical College Hospital. This study was approved by the Ethics Committee of Osaka Medical College, and was performed in accordance with the tenets set forth in the Declaration of Helsinki. Informed written consent was obtained from all subjects prior to the preoperative blood test examination and the vitrectomy being performed.
The mean E2 concentrations (pg/ml) in the male vitreous body samples were ERM: 6.67 ± 4.04, MH: 10.33 ± 7.02, PDR: 4.2 ± 3.05, and RD: 10.00 ± 4.58, while those for the female samples were ERM: 18.82 ± 7.10, MH: 17.00 ± 4.8, PDR: 15.83 ± 3.46, and RD: 16.06 ± 4.57. The mean E2 concentrations in the male serum samples were ERM: 31.67 ± 5.51, MH: 21.00 ± 8.89, PDR: 29.20 ± 7.07, and RD: 24.33 ± 6.51, while those in the female samples were ERM: 5.82 ± 1.08, MH: 7.53 ± 3.2, PDR: 12.75 ± 10.62, and RD: 7.5 ± 4.42. The mean E2 concentration for the males across the four diseases was 6.47 ± 5.72 in the vitreous body and 27.53 ± 7.47 in the serum, while the mean E2 concentration for the females across the four diseases was 16.83 ± 5.37 in the vitreous body and 8.33 ± 6.62 in the serum. In all vitreoretinal diseases, the E2 concentration was significantly higher (P < 0.001) in the serum than in the vitreous body for the males, while conversely, the females exhibited a significantly higher E2 concentration in the vitreous body than in the serum (Fig 1). It has conventionally been thought that sex steroid hormones produced in the gonads, such as E2 and T, as well as glucocorticoid produced in the adrenal cortex, are not synthesized in the brain but are rather transported to the brain, and in particular the hypothalamus, by the blood, producing an effect on nerve cells (hypothalamic pituitary adrenal/gonadal axis) . In other words, it was believed that the brain was simply the target organ of steroid hormones produced from what began as cholesterol in the peripheral gonads and adrenal glands. Source: http://doi.org/10.1371/journal.pone.0180933