Calcium buffer proteins are specific markers of human retinal neurons

Abstract

Ca(2+)-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca(2+)-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists. Moreover, the shortage of well-preserved human samples greatly impedes human retina studies at the cellular and network level. Our purpose has therefore been to examine the distribution of major CaBPs, including calretinin, calbindin-D28, parvalbumin and the recently discovered secretagogin in exceptionally well-preserved human retinal samples. Based on a combination of immunohistochemistry, Neurolucida tracing and Lucifer yellow injections, we have established a database in which the CaBP marker composition can be defined for morphologically identified cell types of the human retina. Hence, we describe the full CaBP make-up for a number of human retinal neurons, including HII horizontal cells, AII amacrine cells, type-1 tyrosine-hydroxylase-expressing amacrine cells and other lesser known neurons. We have also found a number of unidentified cells whose morphology remains to be characterised. We present several examples of the colocalisation of two or three CaBPs with slightly different subcellular distributions in the same cell strongly suggesting a compartment-specific division of labour of Ca(2+)-buffering by CaBPs. Our work thus provides a neurochemical framework for future ophthalmological studies and renders new information concerning the cellular and subcellular distribution of CaBPs for experimental neuroscience.

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

“…In both group 1 and 2 retinas, some of the CaR expressing ACs displayed lobular-like dendritic profiles characteristic of AII ACs ( Figure 6 ). In fact, AII cells have been shown to express CaR in a number of mammalian species, including the cat, the monkey, and the rabbit (Völgyi et al, 1997; Massey and Mills, 1999; Mills and Massey, 1999; Kolb et al, 2002; Kántor et al, 2016b). Thus, we suspect that CaR positive neurons of all group 1 and 2 species that display AII-like soma- and dendrite morphology were AII cells as well.…”

“…We found many CaR-Cx36 double labels in the IPL, particularly in the proximal ON sublamina where AII AC transversal processes form Cx36 GJs with each other or with ON cone bipolar cell axons ( Figure 6 ). Given the fact that AII ACs express CaR in group 1 animal retinas (Völgyi et al, 1997; Massey and Mills, 1999; Mills and Massey, 1999; Kolb et al, 2002; Kántor et al, 2016b) it is very likely that most of the observed double labels represent AII GJ contacts (Kántor et al, 2017). …”

“…CaR has been demonstrated to specifically label AII ACs in most mammalian species (rabbit – Völgyi et al, 1997; Massey and Mills, 1999; monkey – Mills and Massey, 1999; cat – Goebel and Pourcho, 1997; human – Kántor et al, 2016b; Lee et al, 2016), whereas starburst but not AII ACs express CaR in the rat and the mouse retina (Gábriel and Witkovsky, 1998; Haverkamp and Wässle, 2000). These observations were confirmed here showing that AII ACs in the rabbit, cat, and monkey retina express CaR, whereas AII ACs in the rat and the mouse did not.…”

Comparison of cellular localisation of the Ca2+‐binding proteins calbindin, calretinin and parvalbumin in the retina of four different Macaca species

“…Based on these data, cell type‐specific expression is used as a tool to characterise neuronal subpopulations (Baimbridge, Celio, & Rogers, ). A lot of immunohistochemical studies investigating the expression of Ca 2+ ‐binding proteins have been performed using different vertebrate retinae, among them the mouse, rabbit, cat and primate (including human) retina (Chiquet, Dkhissi‐Benyahya, & Cooper, ; Haverkamp & Wässle, ; Kántor et al, ; Röhrenbeck, Wässle, & Heizmann, ). Although there are a lot of similarities between different species, a species‐specific expression has been observed in some cases.…”

Spatial Expression Pattern of the Major Ca2+-Buffer Proteins in Mouse Retinal Ganglion Cells

“…Vision is the most important perception modality for humans, however, it is still not entirely known how the Ca 2+ homeostasis of neurons in the visual signaling axis is controlled by the various neuronal Ca 2+ -buffer proteins (CaBPs). One of the most extensively studied brain loci in this regard is the mammalian retina where expression of CaBPs has been described in many different neuron populations of various model animals [1] and also in a human specimen [2]. Retinal ganglion cells (RGCs) serve as the only output of the retina, and besides simple integration of the converging inputs, they preprocess information prior to relaying it to higher visual brain centers.…”