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Cone and rod cells have different target preferences in vitro as revealed by optical tweezers.

Clarke RJ, Högnason K, Brimacombe M, Townes-Anderson E - Mol. Vis. (2008)

Bottom Line: Cell orientation of the photoreceptor also did not affect preferences: Cells oriented away from dendritic processes could reorient their axonal pole toward the target cell.Cone cells preferred normal partners, and rod cells preferred novel partners.Further,these differences may help explain the patterns of photoreceptor sprouting seen in retinal degeneration in which rod, but not cone, cells invade the inner retinal layers where third-order neurons are located.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neuroscience, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT

Purpose: When neural circuits are damaged in adulthood, regenerating and sprouting processes must distinguish appropriate targets to recreate the normal circuitry. We tested the ability of adult nerve cells to target specific cells in culture using the retina as a model system.

Methods: Under sterile culture conditions, retinal cells, isolated from tiger salamander retina, were micromanipulated with optical tweezers to create pairs of first-order photoreceptor cells with second- or third-order retinal neurons. The development of cell contact and presynaptic varicosities, the direction and amount of neuritic growth, and nerve cell polarity were assessed after seven days in vitro. Cultures were labeled for rod opsin to distinguish rod from cone cells and for the alpha subunit of the trimeric G protein Go (Go alpha) to identify cone-dominated and mixed rod-cone ON bipolar cells.

Results: Quantitative analysis of growth demonstrated that target preferences were cell-specific: Cone cells preferred second-order bipolar cells, whereas rod cells grew toward third-order neurons, which include amacrine and ganglion cells. In addition, when rod cells grew toward bipolar cells, they chose an abnormally high number of Go alpha-positive bipolar cells. These growth patterns were not affected by tweezers manipulation or the amount of growth. Cell orientation of the photoreceptor also did not affect preferences: Cells oriented away from dendritic processes could reorient their axonal pole toward the target cell.

Conclusions: Cone cells preferred normal partners, and rod cells preferred novel partners. These intrinsic preferences indicate that adult nerve cells can have differing capacities for targeting even if they come from the same cell class. Further,these differences may help explain the patterns of photoreceptor sprouting seen in retinal degeneration in which rod, but not cone, cells invade the inner retinal layers where third-order neurons are located.

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Related in: MedlinePlus

Attraction and repulsion of rod and cone neuritic growth to novel partners may contribute to the remodeling of retinal circuits in disease. In disease, as in vitro, rod cells are attracted to multipolar cells that lie in the inner nuclear layer (INL), whereas cone cells tend to form new growth near adjacent bipolar cells. Black arrows indicate normal axonal processes of photoreceptor cells in the retina; green arrows show new growth made in retinal disease. Other abbreviations used: OPL, outer plexiform layer; ONL, outer nuclear layer.
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f7: Attraction and repulsion of rod and cone neuritic growth to novel partners may contribute to the remodeling of retinal circuits in disease. In disease, as in vitro, rod cells are attracted to multipolar cells that lie in the inner nuclear layer (INL), whereas cone cells tend to form new growth near adjacent bipolar cells. Black arrows indicate normal axonal processes of photoreceptor cells in the retina; green arrows show new growth made in retinal disease. Other abbreviations used: OPL, outer plexiform layer; ONL, outer nuclear layer.

Mentions: Although the controlled environment of cell culture mimics intact tissue imperfectly, there is a striking parallel between our in vitro findings and the in vivo growth of photoreceptors in degenerating retina. In early stages of degeneration, rod cells grow extensive processes with varicosities out to the inner retina, where the dendrites of the third-order neurons lie. Sprouting from rod cells toward the inner retina is a robust phenomenon, seen in many forms of the human hereditary retinal disease, RP, in human retinal injury, in aging, and in human retinas with detachment and reattachment (for a review, see [12]). This pathology has been replicated in a cat model of retinal detachment/reattachment [67] and in an amphibian model of the autosomal-dominant form of RP [68]. Studies in human retinas and animal models have demonstrated that the presence of the normal target cells, bipolar and horizontal cells, does not deter rod cell neurites from seeking out inner retinal neurons. In contrast, human cone cells do not form extensive outgrowths into the inner retina. Further, in mouse and porcine animal models of RP, cone cells appear to form new synaptic connections with rod bipolar cells, Goα-containing cells (in mammals, all rod bipolars express Goα), in the outer plexiform layer [69] whereas mouse rod cells contact cone bipolars [70]. Thus, the preferences seen for growth in a controlled in vitro environment mimic the pattern for new sprouts in vivo (Figure 7) and suggest that cell-intrinsic mechanisms contribute to targeting observed in vivo.


Cone and rod cells have different target preferences in vitro as revealed by optical tweezers.

Clarke RJ, Högnason K, Brimacombe M, Townes-Anderson E - Mol. Vis. (2008)

Attraction and repulsion of rod and cone neuritic growth to novel partners may contribute to the remodeling of retinal circuits in disease. In disease, as in vitro, rod cells are attracted to multipolar cells that lie in the inner nuclear layer (INL), whereas cone cells tend to form new growth near adjacent bipolar cells. Black arrows indicate normal axonal processes of photoreceptor cells in the retina; green arrows show new growth made in retinal disease. Other abbreviations used: OPL, outer plexiform layer; ONL, outer nuclear layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2383278&req=5

f7: Attraction and repulsion of rod and cone neuritic growth to novel partners may contribute to the remodeling of retinal circuits in disease. In disease, as in vitro, rod cells are attracted to multipolar cells that lie in the inner nuclear layer (INL), whereas cone cells tend to form new growth near adjacent bipolar cells. Black arrows indicate normal axonal processes of photoreceptor cells in the retina; green arrows show new growth made in retinal disease. Other abbreviations used: OPL, outer plexiform layer; ONL, outer nuclear layer.
Mentions: Although the controlled environment of cell culture mimics intact tissue imperfectly, there is a striking parallel between our in vitro findings and the in vivo growth of photoreceptors in degenerating retina. In early stages of degeneration, rod cells grow extensive processes with varicosities out to the inner retina, where the dendrites of the third-order neurons lie. Sprouting from rod cells toward the inner retina is a robust phenomenon, seen in many forms of the human hereditary retinal disease, RP, in human retinal injury, in aging, and in human retinas with detachment and reattachment (for a review, see [12]). This pathology has been replicated in a cat model of retinal detachment/reattachment [67] and in an amphibian model of the autosomal-dominant form of RP [68]. Studies in human retinas and animal models have demonstrated that the presence of the normal target cells, bipolar and horizontal cells, does not deter rod cell neurites from seeking out inner retinal neurons. In contrast, human cone cells do not form extensive outgrowths into the inner retina. Further, in mouse and porcine animal models of RP, cone cells appear to form new synaptic connections with rod bipolar cells, Goα-containing cells (in mammals, all rod bipolars express Goα), in the outer plexiform layer [69] whereas mouse rod cells contact cone bipolars [70]. Thus, the preferences seen for growth in a controlled in vitro environment mimic the pattern for new sprouts in vivo (Figure 7) and suggest that cell-intrinsic mechanisms contribute to targeting observed in vivo.

Bottom Line: Cell orientation of the photoreceptor also did not affect preferences: Cells oriented away from dendritic processes could reorient their axonal pole toward the target cell.Cone cells preferred normal partners, and rod cells preferred novel partners.Further,these differences may help explain the patterns of photoreceptor sprouting seen in retinal degeneration in which rod, but not cone, cells invade the inner retinal layers where third-order neurons are located.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neuroscience, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT

Purpose: When neural circuits are damaged in adulthood, regenerating and sprouting processes must distinguish appropriate targets to recreate the normal circuitry. We tested the ability of adult nerve cells to target specific cells in culture using the retina as a model system.

Methods: Under sterile culture conditions, retinal cells, isolated from tiger salamander retina, were micromanipulated with optical tweezers to create pairs of first-order photoreceptor cells with second- or third-order retinal neurons. The development of cell contact and presynaptic varicosities, the direction and amount of neuritic growth, and nerve cell polarity were assessed after seven days in vitro. Cultures were labeled for rod opsin to distinguish rod from cone cells and for the alpha subunit of the trimeric G protein Go (Go alpha) to identify cone-dominated and mixed rod-cone ON bipolar cells.

Results: Quantitative analysis of growth demonstrated that target preferences were cell-specific: Cone cells preferred second-order bipolar cells, whereas rod cells grew toward third-order neurons, which include amacrine and ganglion cells. In addition, when rod cells grew toward bipolar cells, they chose an abnormally high number of Go alpha-positive bipolar cells. These growth patterns were not affected by tweezers manipulation or the amount of growth. Cell orientation of the photoreceptor also did not affect preferences: Cells oriented away from dendritic processes could reorient their axonal pole toward the target cell.

Conclusions: Cone cells preferred normal partners, and rod cells preferred novel partners. These intrinsic preferences indicate that adult nerve cells can have differing capacities for targeting even if they come from the same cell class. Further,these differences may help explain the patterns of photoreceptor sprouting seen in retinal degeneration in which rod, but not cone, cells invade the inner retinal layers where third-order neurons are located.

Show MeSH
Related in: MedlinePlus