Immunocytochemical distribution of WARP (von Willebrand A domain-related protein) in the inner ear

Abstract

The basic components of the epithelial, perineural and perivascular basement membranes in the inner ear have been well-documented in several animal models and in the human inner ear. The von Willebrand A domain-related protein (WARP) is an extracellular matrix molecule with restricted expression in cartilage, and a subset of basement membranes in peripheral nerves, muscle and central nervous system vasculature. It has been suggested that WARP have an important role in maintaining the blood-brain barrier. To date no studies on WARP distribution have been performed in the inner that is equipped with an intricate vasculature network. In the present study we determined the distribution of WARP by immunocytochemistry in the human inner ear using auditory and vestibular endorgans microdissected from human temporal bones obtained at autopsy. All subjects (n=5, ages 55-87 years old) had documented normal auditory and vestibular function. We also determined the WARP immunolocalization in the mouse inner ear. WARP-immunoreactivity localized to the vasculature throughout the stroma of the cristae ampullaris, the maculae utricle and saccule in the human and mouse. In the human and mouse inner ear, WARP-immunoreactivity delineated blood vessels located in the stria vascularis, spiral ligament, sub-basilar region, stromal tissue, and the spiral and vestibular ganglia. The distinct localization of WARP in the inner ear vasculature suggests an important role in maintaining its integrity. In addition, WARP allows delineation of microvessels in the inner ear allowing the study of vascular pathology in the development of otological diseases.

WARP: A Unique Extracellular Matrix Component of Cartilage, Muscle, and Endothelial Cell Basement Membranes

“…WARP‐immunoreactivity localized to the vasculature of the cochlea, stria vacularis, and vestibular apparatus with some co‐localization with smooth muscle actin. Consistent with an earlier study (Allen et al, ), WARP was detected in the vessels associated with neural tissue of the brainstem and cerebellar cortex (Duong et al, ).The authors speculate that WARP may have a structural or maintenance role of the blood vessels of the cochlea and vestibule.…”

“…WARP was detected in the inner ear by immunohistochemistry in human autopsy specimens and in mice (Duong et al, ). WARP‐immunoreactivity localized to the vasculature of the cochlea, stria vacularis, and vestibular apparatus with some co‐localization with smooth muscle actin.…”

Immunohistochemical techniques for the human inner ear

“… (1) Present study, (2) Ishiyama et al (2009), (3) Lopez et al (2007), (4) Nadol et al (1993), (5) Robertson et al (2006), (6) Duong et al (2011), (7) Ying and Balaban (2009), (8) Markaryan et al (2009), (9) Ishiyama et al (1994), (10) Anniko et al (1989a), (11) Khalifa et al (2003), (12) Keithley et al (1995), (13) Schrott-Fischer et al (1994), (14) Liu et al (2009), (15) Takahashi et al (2010), (16) Popper et al (2002), (17) Yamashita et al (1991), (18) Yamashita et al (1992), (19) Shi et al (1992a, b), (20) Anniko et al (1989b), (21) Doherty and Linthicum (2004), (22) Keithley et al (2001), (23) Kong et al (1998), (24) Markaryan et al (2008c), (25) Ahmed et al (2013), (26) Balaker et al (2013), (27) Nguyen et al (2014), (28) Vorasubin et al (2016) +Tested and detected by IHC or IF (present study), − not detected in the present study, NR not reported …”

“…The characteristics and specificity of the antibodies used in this study have been described in detail (Duong et al 2011; Ishiyama et al 2009, 2010; Lopez et al 2005a, 2007a, 2009; Calzada et al 2012a, b; Balaker et al 2013; Ahmed et al 2013; Nguyen et al 2014; Vorasubin et al 2016) (Table 3). …”

Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of Meniere’s Disease Patients

“…This likely reflects the severe degeneration of the endothelial cell. While isolectin IB4 identifies capillaries, small and medium sized arteries can be identified with von Willebrand A domain-related protein ( Duong et al, 2011 ). Similarly, in surgical normative acoustic neuroma, the IB4-IF was noted in red, with stellate, fingerlike pericyte processes in green ( Figure 4C ) but the Meniere’s specimen lacked IB4 fluorescence ( Figure 4D ).…”