Recent Advances in Adenosine-to-Inosine RNA Editing in Cancer.

RNA epigenetics, or epitranscriptome, is a growing group of RNA modifications historically classified into two categories: RNA editing and RNA modification. RNA editing is usually understood as post-transcriptional RNA processing (except capping, splicing and polyadenylation) that changes the RNA nucleotide sequence encoded by the genome. This processing can be achieved through the insertion or deletion of nucleotides or deamination of nucleobases, generating either standard nucleotides such as uridine (U) or the rare nucleotide inosine (I). Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent type of RNA modification in mammals and is catalyzed by adenosine deaminase acting on the RNA (ADAR) family of enzymes that recognize double-stranded RNAs (dsRNAs). Inosine mimics guanosine (G) in base pairing with cytidine (C), thereby A-to-I RNA editing alters dsRNA secondary structure. Inosine is also recognized as guanosine by the splicing and translation machineries, resulting in mRNA alternative splicing and protein recoding. Therefore, A-to-I RNA editing is an important mechanism that causes and regulates "RNA mutations" in both normal physiology and diseases including cancer. In this chapter, we reviewed current paradigms and developments in the field of A-to-I RNA editing in the context of cancer.

Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

Bilateral juvenile open angle glaucoma in two Chinese children: case report.

Two cases of bilateral juvenile open angle glaucoma (JOAG) in a four-year-old Chinese boy and a 12-year-old Chinese girl are reported. Applanation tonometry revealed elevated intraocular pressure (IOP) in both eyes. The patients were asymptomatic and bilateral open angle glaucoma was confirmed by a paediatric ophthalmologist. One patient had surgery (trabeculectomy), while the other was treated with topical medication. The early detection and treatment of JOAG is essential for the preservation of vision. Tonometry must be performed as part of a routine eye examination regardless of the age of the patient.

Use of the Optomap with lid retraction and its sensitivity and specificity.

BACKGROUND: Optomap uses the ultra-wide field scanning laser ophthalmoscopy to provide retinal examination. It permits fundus examination without the use of a mydriatic, which is more comfortable for the patients. This paper determines the sensitivity and specificity of the Optomap for detecting retinal signs under non-mydriatic conditions. METHODS: Fifty-four eyes identified with retinal/choroidal signs and eight normal eyes were recruited from 31 Hong Kong Chinese subjects. Photo-documentation of fundal changes was obtained with the Optomap under non-mydriatic conditions before a dilated fundus examination by a clinician using standard procedures. The eyelid was retracted using a cotton bud when necessary. Dilated fundus examinations were performed by another clinician using binocular indirect ophthalmoscopy and slitlamp biomicroscopy with a fundus lens. The Optomap images were evaluated by four other investigators under masked condition. The International Classification of Disease, Ninth Revision (ICD-9-CM) was adopted for recording retinal features. Screening results were compared with those obtained using the dilated fundus examination as the gold standard. RESULTS: The cotton bud method for eyelid retraction showed an improvement in the area of retina that could be visualised. The sensitivity and specificity of the Optomap averaged 76.4 and 71.9 per cent, respectively. Some fundal signs were missed by all observers in the Optomap but not with the biomicroscope. These included white-without-pressure, lattice degeneration, paramacular drusen and pigmentary changes at central fundus. CONCLUSION: Optomap serves as a reliable screening tool for fundus examination especially because it covers a much wider area of the peripheral retina than other digital instruments for fundus photography.

Corneal foreign body injury during overnight orthokeratology lens wear: a case report.

PURPOSE: A case of asymptomatic corneal foreign body injury during orthokeratology lens wear is reported. CASE REPORT: An 8-year-old Chinese female myopic child with 21 months of overnight orthokeratology lens wear experienced a corneal foreign body injury without symptoms. The foreign body was removed and the eye treated with prophylactic antibiotic and ocular lubricant. Orthokeratology treatment was resumed 4 weeks after initial detection and management and a small residual corneal scar remained. DISCUSSION: The mechanisms, differential diagnoses, management and role of neural sensitivity in corneal foreign body injury during orthokeratology lens wear are discussed. Clinicians should be aware that subtle corneal insult may be without symptoms during prolonged overnight orthokeratology lens wear.

Central corneal epitheliopathy in a long-term, overnight orthokeratology lens wearer: a case report.

PURPOSE: The purpose of this study is to report an unusual case of central corneal epitheliopathy (CCE) in a long-term orthokeratology lens wearer. CASE REPORT: A single observational case report of a 12-year-old Chinese female myope with 3(1/2) years' experience in wearing orthokeratology lenses overnight was diagnosed with a CCE lesion during her regular orthokeratology aftercare consultation. The patient was asymptomatic. Trace or almost negative fluorescein staining was observed over the particular lesion area and, according to the clinical features of the corneal lesion, was thought to be a partially formed "dellen." The lesion healed after the use of the orthokeratology lenses was suspended for 4 months and reappeared when the patient resumed wearing the lenses. Close monitoring of the corneal condition was needed on this patient, and permanent discontinuation of the orthokeratology procedures will be considered if the signs and symptoms of the lesion worsen. DISCUSSION: The etiology, clinical management and the possible differential diagnosis of the central cornea "dellen" are discussed. CONCLUSION: A central corneal "dellen" may be associated with long-term, overnight use of orthokeratology lenses.

The performance of four different corneal topographers on normal human corneas and its impact on orthokeratology lens fitting.

PURPOSE: To evaluate the performances of Humphrey Atlas 991, Orbscan II, Dicon CT200, Medmont E300 on young Chinese adults. METHODS: Three sets of corneal topography measurements were obtained from each topographer from 22 subjects-two sets by the same examiner and one set by another examiner on the same day. RESULTS: There were no significant within-examiner and between-examiner differences for any of the parameters tested for each topographer. However, only the repeatability and reproducibility (of apical radius[Ro], eccentricity, and elevation) of the Humphrey and Medmont were good. There was no statistically significant between-topographer difference in R(o), but significant differences in eccentricity and elevation values were found. The number of repeated readings that should be taken for a precision of 2 microm (elevation) were 12 for the Humphrey and 2 for the Medmont. CONCLUSIONS: The performance of both the Humphrey and the Medmont was very good. R(o) and eccentricity values of different topographers cannot be used interchangeably, but the agreement in elevation values was good for these topographers. The number of repeated readings required for maximum precision varies with the topographer used, and they are not interchangeable.