Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions.

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

The role of transforming growth factor beta in myopia development.

Myopia is widely recognized as an epidemic. Studies have found a link between Transforming Growth Factor-beta (TGF-ß) and myopia, but the specific molecular mechanisms are not fully understood. In this study, a monocular model in tree shrews (Tupaia belangeri) was established to verify the molecular mechanism of TGF-ß in myopia. The results indicated that there were significant changes in TGF-ßs during the treatment of myopia, which could enhance the refractive ability and axial length of the eye. Immunohistochemical staining, real-time fluorescent quantitative PCR, and immunoblotting results showed a significant upregulation of MMP2 and NF-κB levels, and a significant downregulation of COL-I expression in the TGF-ß treated eyes, suggesting that NF-κB and MMP2 are involved in the signaling pathways of TGF-ßs induced myopia and axial elongation. Moreover, the expression levels of IL-6, IL-8, MCP-1, IL-1ß, TNF-α, TAK1, and NF-κB in the retina were all significantly elevated. This indicates that TGF-ß stimulates the inflammatory response of retinal pigment epithelial cells through the TAK1-NF-κB signaling pathway. In conclusion, this study suggests that TGF-ß promotes the progression of myopia by enhancing intraocular inflammation.

Acupuncture modulates development of myopia by reducing NLRP3 inflammasome activation via the dopamine-D1R signaling pathway.

BACKGROUND: Dopamine has been suggested to be a stop signal for eye growth and affects the development of myopia. Acupuncture is known to increase dopamine secretion and is widely used to treat myopia clinically. OBJECTIVE: The aim of this study was to determine if acupuncture inhibits myopia progression in form deprived Syrian hamsters by inducing rises in dopamine content that in turn suppress inflammasome activation. METHODS: Acupuncture was applied at LI4 and Taiyang every other day for 21 days. The levels of molecules associated with the dopamine signaling pathway, inflammatory signaling pathway and inflammasome activation were determined. A dopamine agonist (apomorphine) was used to evaluate if activation of the dopaminergic signaling pathway suppresses myopia progression by inhibiting inflammasome activation in primary retinal pigment epithelial (RPE) cells. A dopamine receptor 1 (D1R) inhibitor (SCH39166) was also administered to the hamsters. RESULTS: Acupuncture inhibited myopia development by increasing dopamine levels and activating the D1R signaling pathway. Furthermore, we also demonstrated that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome activation was inhibited by activation of the D1R signaling pathway. CONCLUSION: Our findings suggest that acupuncture inhibits myopia development by suppressing inflammation, which is initiated by activation of the dopamine-D1R signaling pathway.

Efficacy And Safety Of Travoprost Versus Timolol To Treat Early-Onset Ocular Hypertension Secondary To Vitrectomy: A Randomized Trial.

PURPOSE: To evaluate the efficacy and safety of travoprost 0.004% versus timolol 0.5% as an initial intraocular pressure (IOP)-lowering medication for ocular hypertension secondary to vitrectomy. PATIENTS AND METHODS: We performed a randomized, controlled, observer-blinded clinical trial in the Eye & ENT Hospital of Fudan University in China. This trial was registered at www.chictr.org.cn (ChICTR1800014942) before patient enrollment. Seventy-nine adults with IOP of 25-45 mmHg secondary to vitrectomy in the latest one month were enrolled and randomized to receive travoprost 0.004% or timolol 0.5%. More drugs were administered to patients with IOP > 25 mmHg during follow-up. RESULTS: The mean IOP reduction at day 1 was -10.97 mmHg in the timolol group and -15.02 mmHg in the travoprost group (P = 0.006); no significant difference was observed between the groups at later time points. The number of IOP-lowering medications at day 21 was 0.64 in the timolol group and 1.15 in the travoprost group (P = 0.038), while no significant differences were observed at other time points. The proportion of single IOP-lowering medications used during the 4-week follow-up was 72.73% in the timolol group and 68.42% in the travoprost group (P = 0.692). Inflammation scores were not significantly different in the two groups at any time point. Increased ocular hyperemia occurred in 8 patients (19%) in the travoprost group and none in the timolol group (P = 0.005). There were no significant differences in other adverse events between the two groups. After logistic regression model analysis, IOP ≥ 30 mmHg, inflammation score ≥ 2, and silicone oil as tamponade were found to be the factors with significant effects on the number of IOP-lowering medications used during the 4-week follow-up. CONCLUSION: Travoprost and timolol have similar efficacy and safety for treating ocular hypertension secondary to vitrectomy.

Trends in the characteristics of vitrectomy in Eastern China.

BACKGROUND: Several new instruments and techniques for pars plana vitrectomy (PPV) have been widely used in recent years, but information about the related characteristics of PPV in China is limited. To investigate the trends in the characteristics of PPV in Eastern China, an 8-year retrospective study was conducted. PATIENTS AND METHODS: We collected data from patients who underwent PPV at the Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai, China, in November 2007, November 2011, and November 2015. Cases of trauma-related retinopathy were excluded. Data on the patient demographics, surgical procedures, and the prophylactic use of IOP-lowering medications were collected and analyzed. RESULTS: In 2015, most PPVs were conducted with a 23-gauge system, whereas all PPVs in 2007 and 2011 were conducted with a 20-gauge system. The proportions of macular disease in the population in 2007, 2011, and 2015 were 9.1%, 10.7%, and 21.5%, respectively (P<0.001). The proportion of PPV that was combined with lens extraction and intraocular lens (IOL) implantation increased significantly from 12.81% in 2007 to 25.95% by 2015 (P<0.001). The proportions of patients treated with IOP-lowering drugs in 2007, 2011, and 2015 were 27.40%, 38.20%, and 12.60%, respectively (P<0.001). In 2007, systemic carbonic anhydrase inhibitors (CAI-Ss) and beta blockers (BBs) were the two main types of prophylactic IOP-lowering drugs administered, but their use had decreased in 2015 (P<0.001). The preventive use of adrenergic agonists (AAs), topical carbonic anhydrase inhibitors (CAI-Ts), and prostaglandin analogs (PGAs) became increasingly frequent from 2007 to 2015 (P<0.05). CONCLUSION: The 23-gauge system, rather than the 20-gauge system, had become the mainstream PPV instrument by 2015. The proportion of macular disease patients requiring PPV in China clearly increased, and the rate of prophylactic IOP-lowering drug use decreased by 2015.