Collection 01 October 2019

Focus on the Eye

The editors of Laboratory Investigation and Modern Pathology present a variety of recent papers related to ocular pathology. These experimental and diagnostic studies cover congenital anomalies, corneal injury and repair, degenerative disease, and various malignancies.

Content

Histone H2B induces retinal ganglion cell death through toll-like receptor 4 in the vitreous of acute primary angle closure patients

Increased levels of histone H2B (H2B), a damage-associated protein, are found in the vitreous of patients with acute primary angle closure. Elevated H2B causes severe inflammation and subsequent retinal ganglion cell death through toll-like receptor 4 (TLR4) signaling. These results provide new insight for the mechanism of retinal ganglia degeneration.
- Yasunari Munemasa
ArticleOpen Access22 Apr 2020 Laboratory Investigation
Shp2-mediated MAPK pathway regulates ΔNp63 in epithelium to promote corneal innervation and homeostasis

In this paper, the authors found that conditional ablation of Shp2 in mouse K14-positive corneal epithelium (Shp2^K14ce-cko) impairs corneal innervation and results in corneal epithelial thinning, which resembles neurotrophic keratopathy. Furthermore, the data indicate that Shp2 signaling plays a pivotal role in corneal epithelial homeostasis.
- Yuka Okada
- Yujin Zhang
- Chia-Yang Liu
Article25 Oct 2019 Laboratory Investigation
TRPC5 regulates axonal outgrowth in developing retinal ganglion cells

This study shows that TRPC5 is an important negative regulator of retinal ganglion cell (RGC) axonal outgrowth and an important regulator of neurite remodeling. The authors hypothesize that TRPC5 senses abnormal intraocular pressure changes and contributes to the death of RGCs in disease. In glaucoma, for example, excessive Ca2+ entry through TRPC5 might induce dendritic and axonal remodeling, which could lead to cell death.
- Mai Oda
- Hanako Yamamoto
- Koji Shibasaki
Article16 Dec 2019 Laboratory Investigation
Vascular changes in diabetic retinopathy—a longitudinal study in the Nile rat

In this paper, the authors dissected the temporal sequence of three early events in diabetic retinopathy. They show that vascular degeneration is the initiating cellular change during the development of retinopathy in the diabetic Nile rat. Focusing on vascular events, they conducted a detailed longitudinal study and showed that the Nile rat exhibits a wide range of retinal lesions remarkably similar to the human condition.
- Huishi Toh
- Alexander Smolentsev
- James A. Thomson
Technical Report17 May 2019 Laboratory Investigation
Conjunctival ‘mucoepidermoid carcinoma’ revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye
- Hardeep S. Mudhar
- Tatyana Milman
- Ian G. Rennie
Article13 Jan 2020 Modern Pathology
Human papillomavirus type 16 causes a defined subset of conjunctival in situ squamous cell carcinomas
- Heather Griffin
- Hardeep Singh Mudhar
- John Doorbar
ArticleOpen Access4 Sep 2019 Modern Pathology
Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles
- Simon Andreasen
- Qihua Tan
- Preben Homøe
Article21 Feb 2018 Modern Pathology
Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies
- Andi K Cani
- Moaaz Soliman
- Rajesh C Rao
Original Article22 Apr 2016 Modern Pathology
Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice

Homeostasis of the corneal epithelium is critical in exerting a barrier function to noxious external stimuli. This study shows that that plakoglobin, a member of the catenin protein family, is essential to the maintenance of homeostasis of the corneal epithelium in mice. Corneal epithelium-specific deletion of the plakoglobin gene impairs tissue integrity against mechanical intervention and also suppresses wound healing without affecting cell proliferation.
- Masahide Kokado
- Masayasu Miyajima
- Shizuya Saika
Article25 May 2018 Laboratory Investigation
Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4

The trigeminal sensory nerve is critical for maintenance of corneal epithelial stem cells in the corneal limbus and is essential to the homeostasis of the tissue. TRPV4 signal mediated gene expression in the nerve drives expression of stem cell markers and nerve growth factor in the limbal stem cells as well as potentiates their proliferation.
- Yuka Okada
- Takayoshi Sumioka
- Shizuya Saika
Article9 Nov 2018 Laboratory Investigation
Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma
- Pablo Zoroquiain
- Evangelina Esposito
- Miguel N. Burnier
Article26 Mar 2018 Modern Pathology
The biological and prognostic significance of angiotropism in uveal melanoma
- Raymond L Barnhill
- Mengliang Ye
- Claire Lugassy
Research Article27 Feb 2017 Laboratory Investigation
Melanoma subtypes demonstrate distinct PD-L1 expression profiles
- Genevieve J Kaunitz
- Tricia R Cottrell
- Janis M Taube
Research Article24 Jul 2017 Laboratory Investigation
Combined mutation and copy-number variation detection by targeted next-generation sequencing in uveal melanoma
- Kyra N Smit
- Natasha M van Poppelen
- Emine Kiliç
Original Article12 Jan 2018 Modern Pathology
Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway
- Wenting Yu
- Ziyan Yu
- Jiangyue Zhao
ArticleOpen Access25 Jan 2019 Laboratory Investigation
Establishment of an in vitro monolayer model of macular corneal dystrophy
- Sumit Murab
- Shibu Chameettachal
- Sourabh Ghosh
Research Article17 Oct 2016 Laboratory Investigation
Protective effects of an HTRA1 insertion–deletion variant against age-related macular degeneration in the Chinese populations
- Tsz Kin Ng
- Xiao Ying Liang
- Chi Pui Pang
Research Article14 Nov 2016 Laboratory Investigation
Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice
- Hiroki Iwanishi
- Norihito Fujita
- Shizuya Saika
Research Article7 Mar 2016 Laboratory Investigation
Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background
- Jingling Shen
- Dan Shi
- Zhenghua Li
Technical Report14 Mar 2016 Laboratory Investigation
Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin αV
- Yoshiyuki Kobayashi
- Shigeo Yoshida
- Tatsuro Ishibashi
Research Article26 Sep 2016 Laboratory Investigation
Blockade of MDM2 with inactive Cas9 prevents epithelial to mesenchymal transition in retinal pigment epithelial cells

CRISPR/dCas9 blocks TGF-β2-induced mouse double minute 2 (MDM2) expression by targeting its second promoter, without affecting the basal expression. Epithelial to mesenchymal transition is blocked by MDM2 suppression in retinal pigment epithelial cells. In this way, CRIPSR/dCas9 is a promising novel therapy for proliferative vitreoretinopathy without interfering basal gene function.
- Bing Liu
- Jingyuan Song
- Hetian Lei
Article22 Aug 2019 Laboratory Investigation
Rescue of retinal morphology and function in a humanized mouse at the mouse retinol-binding protein locus
- Li Liu
- Tomohiro Suzuki
- Zhenghua Li
Research Article30 Jan 2017 Laboratory Investigation
Mitochondrial localization of PABPN1 in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset myopathy caused by the expansion of polyalanine in the PABPN1 gene. Abnormal accumulation of PABPN1 on the inner membrane of mitochondria was detected in mouse and cell models of OPMD. The localization of expanded PABPN1 in mitochondria may be associated with mitochondrial dysfunction.
- Tsukasa Doki
- Satoshi Yamashita
- Yukio Ando
Article20 Mar 2019 Laboratory Investigation

Focus on the Eye

Content

Histone H2B induces retinal ganglion cell death through toll-like receptor 4 in the vitreous of acute primary angle closure patients

Shp2-mediated MAPK pathway regulates ΔNp63 in epithelium to promote corneal innervation and homeostasis

TRPC5 regulates axonal outgrowth in developing retinal ganglion cells

Vascular changes in diabetic retinopathy—a longitudinal study in the Nile rat

Conjunctival ‘mucoepidermoid carcinoma’ revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye

Human papillomavirus type 16 causes a defined subset of conjunctival in situ squamous cell carcinomas

Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are morphologically and genetically similar but have distinct microRNA expression profiles

Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies

Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice

Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4

Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma

The biological and prognostic significance of angiotropism in uveal melanoma

Melanoma subtypes demonstrate distinct PD-L1 expression profiles

Combined mutation and copy-number variation detection by targeted next-generation sequencing in uveal melanoma

Lens-specific conditional knockout of Msx2 in mice leads to ocular anterior segment dysgenesis via activation of a calcium signaling pathway

Establishment of an in vitro monolayer model of macular corneal dystrophy

Protective effects of an HTRA1 insertion–deletion variant against age-related macular degeneration in the Chinese populations

Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin αV

Blockade of MDM2 with inactive Cas9 prevents epithelial to mesenchymal transition in retinal pigment epithelial cells

Rescue of retinal morphology and function in a humanized mouse at the mouse retinol-binding protein locus

Mitochondrial localization of PABPN1 in oculopharyngeal muscular dystrophy

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