Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma
Introduction
Primary neuron injury has profound effects on synaptically linked distant neurons, and this process is called transsynaptic or transneuronal degeneration. Transsynaptic degeneration is implicated in the dissemination of pathology in diverse neurological disorders including Alzheimer's disease (Su et al., 1997), amyotrophic lateral sclerosis (Kiernan and Hudson, 1991), and brain trauma (Conti et al., 1998). More recently, considerable evidence has accumulated suggesting that damage also is disseminated in this manner in glaucoma (Yücel et al., 2000; Weber et al., 2000; Yücel et al., 2001; Gupta and Yücel, 2000).
Retinal ganglion cell death (RGC) is the major pathological feature in glaucoma, and has been studied extensively at the level of the retina and optic nerve head (Fechtner and Weinreb, 1994). RGCs of various subtypes with specific morphological and functional features (Perry et al., 1984; Perry and Coway, 1984; Kolb, 1991; Dacey, 1996) share a common course as their axons exit the globe in the optic nerve, converge upon the chiasm, form the optic tract, and terminate predominantly in the lateral geniculate nucleus (LGN). Function-specific RGC terminals target anatomically distinct readily identifiable LGN layers. The functional channels for the magnocellular (M), parvocellular (P), and koniocellular (K) pathways are neatly separated into motion, red–green, and blue-ON channels, respectively (Hendry and Calkins, 1998). As the major recipient of RGC input (Perry et al., 1984), and the predominant relay station of information to the primary visual cortex, studies of the neurons of the LGN and visual cortex characterize the specific visual pathways affected in glaucoma. There is accumulating evidence for neurochemical (Vickers et al., 1997), metabolic (Crawford et al., 2000; Crawford et al., 2001), functional (Smith et al., 1993) and degenerative changes (Yücel et al., 2000; Weber et al., 2000; Yücel et al., 2001) of the CNS in glaucoma.
The experimental monkey model of glaucoma is a good model for the investigation of CNS changes in glaucoma. The retinal and optic nerve pathological findings following injury by elevated IOP closely mimic histopathological observations in human glaucoma (Quigley et al., 1982; Radius and Pederson, 1984; Yücel et al., 1999). The primate central visual system is well characterized with respect to its fine anatomy, physiology and specific cell markers (Hendry and Calkins, 1998), and has striking similarities to the human visual system. In this paper, we examine the effects of RGC loss on M, P, and K neurons in the LGN and on primary visual cortex in this model of glaucoma.
Section snippets
Lateral geniculate nucleus degeneration in glaucoma
The LGN of each hemisphere represents the contralateral half of the visual field, and is composed of 6 principal layers of neurons. Interneurons are those neurons confined to the LGN, while relay neurons project to the visual cortex (Montero, 1986; Hendry and Calkins, 1998). Three populations of relay neurons have been identified as the M, P, and K types (Schiller et al., 1990; Hendry and Calkins, 1998). M neurons located in the most ventral layers 1 and 2 receive their major retinal input from
Primary visual cortex in glaucoma
The primary visual cortex, responsible for higher order visual processing, is anatomically divided into 6 major layers, from the pial surface to the underlying white matter (I–VI). Cortical layers receiving major LGN input are layers IV and layer II–III. Layer IV is further subdivided into 4 sub-layers, IVA, IVB, IVCα, and IVCβ. M and P relay neurons terminate directly in IVCα and IVCβ, respectively (Lund, 1988). K neurons project directly to “cytochrome oxidase (CO) blobs” in cortical layers
Magnocellular and parvocellular pathway degeneration
In studies using CO histochemistry, metabolic activity in ocular dominance columns driven by the glaucomatous eye is expressed relative to activity seen in ocular dominance columns driven by the non-glaucomatous eye in the same cortex. However, the presence and the extent of this relative change in metabolic activity depends on the balance of activity levels in ocular dominance columns driven by both glaucomatous and non-glaucomatous eyes. Changes in the level of activity in ocular dominance
Implications
CNS damage in glaucoma appears to be proportionate to the extent of optic nerve damage in at least M and P geniculo-cortical pathways. Separate from the retinal and optic nerve insults which underlie it, this CNS damage once obtained, may itself contribute to glaucomatous progression. Lesions of the LGN (Pearson and Stoffler, 1992; Pearson and Thompson, 1993) and cortex (Weller and Kaas, 1989; Johnson and Cowey, 2000) induce loss of RGCs and the degenerating LGN in glaucoma may similarly
Acknowledgements
Supported in part by the E.A. Baker Foundation of the Canadian Institute for the Blind, Toronto, Ontario (YHY), E.A. Baker Foundation of the Canadian Institute for the Blind (NG), Glaucoma Research Society of Canada (NG, YHY), Glaucoma Research Foundation, San Francisco, CA (YHY), The Glaucoma Foundation New York, NY (YHY), National Eye Institute (EY02698, PLK) Research to Prevent Blindness (PLK), Joseph Drown Foundation (RNW), Anewman Memorial Foundation (NG), St. Michael's Hospital Volunteer
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