Abstract
Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin α1, α5, β1, β2 and γ1 to be predominantly expressed in Bruch’s membrane and the inner limiting membrane. Laminin-332 and laminin γ3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin γ3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin γ3 during human retinogenesis.
Highlights
The extracellular matrix (ECM) is a non-cellular structure that is present in all tissues and can be divided into two separate types, the connective tissue matrix and the basement membrane[1]
Distribution of laminins during retinal development and in adult retina We examined the distribution of all existing laminin chains in different adult species, human developing retina, as well as Human pluripotent stem cells (hPSCs)-derived retinal organoids using IHC
Strong immunoreactivity was found in Bruch's membrane (BrM) and inner limiting membrane (ILM) of the mouse retina (Fig. 1a), whereas laminin-332 was expressed throughout the macaque and human retina (Figs. 1b, c)
Summary
The extracellular matrix (ECM) is a non-cellular structure that is present in all tissues and can be divided into two separate types, the connective tissue matrix and the basement membrane[1]. The ECM provides structural support and promotes cellular functions including differentiation, adhesion, migration, proliferation, axonal growth and morphogenesis in many tissues[1,2,3,4]. Laminins (Lam) are a family of heterotrimeric glycoproteins and part of the ECM5 They are a major component of basement membranes and are important for multiple biological processes[4,5]. Laminin-111 and other laminin chains play an important role during optic cup morphogenesis and retinal histogenesis[19,20,21], photoreceptor structure and synapse formation[20,22,23], stability of the inner limiting membrane (ILM)[24] and retinal ganglion cell (RGC) axonal growth[25,26,27,28,29]
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