Application of generative adversarial networks (GAN) for ophthalmology image domains: a survey.

BACKGROUND: Recent advances in deep learning techniques have led to improved diagnostic abilities in ophthalmology. A generative adversarial network (GAN), which consists of two competing types of deep neural networks, including a generator and a discriminator, has demonstrated remarkable performance in image synthesis and image-to-image translation. The adoption of GAN for medical imaging is increasing for image generation and translation, but it is not familiar to researchers in the field of ophthalmology. In this work, we present a literature review on the application of GAN in ophthalmology image domains to discuss important contributions and to identify potential future research directions. METHODS: We performed a survey on studies using GAN published before June 2021 only, and we introduced various applications of GAN in ophthalmology image domains. The search identified 48 peer-reviewed papers in the final review. The type of GAN used in the analysis, task, imaging domain, and the outcome were collected to verify the usefulness of the GAN. RESULTS: In ophthalmology image domains, GAN can perform segmentation, data augmentation, denoising, domain transfer, super-resolution, post-intervention prediction, and feature extraction. GAN techniques have established an extension of datasets and modalities in ophthalmology. GAN has several limitations, such as mode collapse, spatial deformities, unintended changes, and the generation of high-frequency noises and artifacts of checkerboard patterns. CONCLUSIONS: The use of GAN has benefited the various tasks in ophthalmology image domains. Based on our observations, the adoption of GAN in ophthalmology is still in a very early stage of clinical validation compared with deep learning classification techniques because several problems need to be overcome for practical use. However, the proper selection of the GAN technique and statistical modeling of ocular imaging will greatly improve the performance of each image analysis. Finally, this survey would enable researchers to access the appropriate GAN technique to maximize the potential of ophthalmology datasets for deep learning research.

Suppression of Nrf2 signaling by angiotensin II in murine renal epithelial cells.

Angiotensin II (ATII), a physiologically active mediator of the renin-angiotensin system, has been shown to be associated with renal fibrosis pathophysiology. In our current study with murine renal epithelial TCMK-1 cells, ATII inhibited the expression of NF-E2-related factor 2 (Nrf2)-target antioxidant genes such as NAD(P)H: quinone oxidoreductase-1 and γ-glutamate cysteine ligase (GCL). In accord to the reduced expression of GCL, a GSH biosynthesis enzyme, ATII treatment reduced intracellular GSH content and increased the levels of reactive oxygen species (ROS). While, there was no significant changes in nuclear protein levels of Nrf2 following ATII treatment, implying the potential alterations in the expression of partner proteins of Nrf2. Our measurement of Nrf2 partner bZIP transcription factors, including Bach1, small Maf proteins, and activating transcription factor 3 (ATF3) showed that the expression level for ATF3 was enhanced in ATII-treated TCMK cells. Presumably through ATII-induced oxidative stress, ATII treatment was found to enhance the inducible level of TGFß-mediated α-smooth muscle actin (α-SMA) expression, which is one of molecular markers of renal fibrosis. In conclusion, our results indicate that ATII suppresses Nrf2-GSH signaling in murine renal epithelial cells. Elevated ROS levels in ATII exposed epithelial cells might be a causing factor contributing to renal fibrosis pathology.

Transcription factor Nrf2 maintains the basal expression of Mdm2: An implication of the regulation of p53 signaling by Nrf2.

Co-operated regulation of oxidative stress-response transcription factors would be an important issue for animals to determine the cell fate under environmental stress. This notion raises a possibility that NF-E2-related factor 2 (Nrf2), which confers cytoprotection against oxidative stress, and p53 can have a direct co-regulation network. In the current study, we have indentified that the expression of murine double minute 2 (Mdm2) is repressed in nrf2-deleted murine embryonic fibroblasts (MEFs). This was confirmed by microarray, RT-PCR, and immunoblot analyses, and further promoter analysis showed that Nrf2 is directly involved in the basal expression of Mdm2 through the antioxidant response element, which is located in the first intron of this gene. This linkage between Nrf2 and Mdm2 appears to cause the accumulation of p53 protein in nrf2-deficent MEFs. In addition, we show that ovarian carcinoma A2780 cells with Nrf2 shRNA expression displayed higher levels of p53 activation in response to hydrogen peroxide treatment, leading to increased cell death. Collectively, our results suggest novel evidence that the inhibition of Nrf2 can suppress Mdm2 expression, which may result in p53 signaling modulation. In addition, this observation supports the concept that Nrf2 inhibition in cancer cells can facilitate apoptotic response upon environmental stress.

Activation of the Nrf2-antioxidant system by a novel cyclooxygenase-2 inhibitor furan-2-yl-3-pyridin-2-yl-propenone: implication in anti-inflammatory function by Nrf2 activator.

Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is a novel synthetic compound and has demonstrated anti-inflammatory activity by inhibiting cyclooxygenase-2 (COX-2). It is widely accepted that reactive oxygen species (ROS) generated by activated inflammatory cells can exacerbate inflammation. In this study, the potential antioxidative efficacy of FPP-3 has been investigated in murine cells. FPP-3 increased the expression of multiple antioxidative enzymes, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), gamma-glutamylcysteine ligase (GCL) and heme oxygenase-1 (HO-1), by facilitating the nuclear translocation of nuclear factor-erythroid 2-p45-related factor 2 (Nrf2). Inducibility of antioxidant proteins such as HO-1 were lost in nrf2-deficient murine fibroblasts. As a result of enhanced cellular antioxidative capacity, elevation of NF-kappaB-driven reporter gene expression by lipopolysaccharide was attenuated by FPP-3 treatment in murine fibroblasts. Furthermore, FPP-3 treatment inhibited UVA-mediated induction of COX-2 in murine keratinocytes. Our current study suggests that FPP-3, which has been developed as a novel COX-2 inhibitor, has antioxidative properties by activating the Nrf2-ARE pathway. The dual function of this compound may provide a better strategy to block/attenuate the inflammation process and to alleviate ROS-associated inflammatory complications.