Pulmonary Surfactant Protein A Is Expressed in Mouse Retina by Muller Cells and Impacts Neovascularization in Oxygen-Induced Retinopathy

Bhatti, Faizah; Ball, Geneviève; Hobbs, Ronald; Linens, Annette; Munzar, Saad; Akram, Rizwan; Barber, Alistair J.; Anderson, Michael P.; Elliott, Michael H.; Edwards, Madeline

doi:10.1167/iovs.13-13652

Cited by 11 publications

(11 citation statements)

References 60 publications

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“…Retinal and Müller cell SP-A is upregulated via the NFkB pathway and it is up regulated during the hypoxia phase of oxygen-induced retinopathy (OIR). A lack of SP-A attenuates NV in the OIR model and thus, SP-A may be a marker of retinal inflammation during NV (Bhatti et al, 2014). Müller cells also produce PEDF (Pigment epithelium-derived factor), TGF-b and thrombospondin-1 as anti-angiogenic proteins that are important in adjusting the ''angiogenic balance'' (Eichler et al, 2004).…”

Section: Gliosismentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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Section: Gliosismentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

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“…Furthermore, SP-A has been shown to inhibit phospholipase activity in vitro[ 21 ]. Interestingly, in studies employing Sftpa1 -/- mice ( Sftpa1 -/- rd1 +/+ generated by us), we showed that when retinal architecture is preserved that absence of SP-A protein impacts retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR)[ 7 ]. Thus, it appears that the SP-A protein plays a key role of directing early angiogenic/vascular processes but may not impact the neuronal function of the retina.…”

Section: Discussionmentioning

confidence: 99%

“…They are important in recognizing and mediating neutralization of viruses, bacteria and fungi, clearance of apoptotic and necrotic cells, and resolution of inflammation[ 3 – 5 ]. Recently, these molecules have been found in other organ systems aside from the pulmonary system[ 6 ] including vaginal and amniotic fluid, the gastrointestinal tract, renal system and the ocular system[ 7 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Retinal degeneration mutation in Sftpa1tm1Kor/J and Sftpd -/- targeted mice

2018

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Surfactant proteins are important collectin immune molecules with a wide distribution throughout the body, including the ocular system. Mice with gene deletions for the surfactant protein genes Sftpa1 and Sftpd were observed to have visual impairment and thinning of the outer nuclear layers of the retina. We hypothesized that gene deletion of Sftpa1 and Sftpd (Sftpa1tm1Kor/J and Sftpd-/-) results in early retinal degeneration in these mice. Sftpa1tm1Kor/J and Sftpd-/- retinas were evaluated by histopathology and optical coherence tomography (OCT). Retinas from Sftpa1tm1Kor/J and Sftpd -/- mice showed early retinal degeneration with loss of the outer nuclear layer. After screening of mice for known retinal degeneration mutations, the mice were found to carry a previously unrecognized Pde6brd1 genotype which resulted from earlier breeding of the strain with Black Swiss mice during their generation. The mutation was outbred and the genotype of Sftpa1tm1Kor/J and Sftpd-/- was confirmed. Outbreeding of the Pde6brd1 mutation resulted in restoration of normal retinal architecture confirmed by in vivo and in vitro examination. We can therefore conclude that loss of Sftpa1 and Sftpd do not result in retinal degeneration. We have now generated retinal Sftpa1 and Sftpd targeted mice that exhibit normal retinal histology.

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“…LPS from Gram-negative bacteria has been show to induce expression of both SP-A and SP-D (Herbein and Wright, 2001; Saka et al, 2016; Vayrynen et al, 2002) Similarly, our research group has shown that human retinal Müller cells, when exposed to the TLR-2 ligand (PamCy3) and TLR-4 ligand (LPS), showed an up regulation of SP-A protein expression (Bhatti et al, 2015). …”

Section: Interaction Of Molecules With Collectins- Ligands and Recmentioning

confidence: 92%

“…NV is also a hallmark of diabetic retinopathy and sometimes with wet age related macular degeneration. We recently showed that SP-A is present in the mouse retina and appears to be associated with the vasculature of both choroidal and retinal artery distribution (Bhatti et al, 2015). Up-regulation of SP-A protein was seen in both retinal tissues as well in human retinal Müller cells grown in culture.…”

Section: Review Of the Localization And Known Functions Of Extra-pmentioning

confidence: 99%

Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins

Vieira

Kung

Bhatti

2017

Annals of Anatomy - Anatomischer Anzeiger

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The collectins family encompasses several collagenous Ca2+-dependent defense lectins that are described as pathogen recognition molecules. They play an important role in both adaptive and innate immunity. Surfactant protein A and D are two of these proteins which were initially discovered in association with surfactant in the pulmonary system. The structure, immune and inflammatory functions, and genetic variations have been well described in relation to their roles, function and pathophysiology in the pulmonary system. Subsequently, these proteins have been discovered in a wide range of other organs and organ systems. The role of these proteins outside the pulmonary system is currently an active area of research. This review intends to provide a current overview of the genetics, structure and extra-pulmonary functions of the surfactant collectin proteins.

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Pulmonary Surfactant Protein A Is Expressed in Mouse Retina by Muller Cells and Impacts Neovascularization in Oxygen-Induced Retinopathy

Abstract: PURPOSE. Surfactant protein A (SP-A) up-regulates cytokine expression in lung disease of prematurity. Here we present data that for the first time characterizes SP-A expression and localization in the mouse retina and its impact on neovascularization (NV) in the mouse.

Cited by 11 publications

References 60 publications

Glia–neuron interactions in the mammalian retina

Glia–neuron interactions in the mammalian retina

Retinal degeneration mutation in Sftpa1tm1Kor/J and Sftpd -/- targeted mice

Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins

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