Synaptic growth in the rod terminals of mice after partial photoreceptor cell loss: A three-dimensional ultrastructural study

Abstract

Following partial loss of photoreceptor cells in the retina of mice afflicted by mutant genes, damaging light exposure, or old age, some of the remaining rod cells exhibited a process of growth in their synapses with the second order retinal neurons. This growth was recognized by the presence of multiple synaptic sites in some of the rod terminals in the outer plexiform layer. In this study, a comparative analysis of the microanatomical changes in the synaptic structures of the rod terminals in the retina of normal, rds homozygous and heterozygous mutant and light exposed albino mice was undertaken by using a computer‐aided three‐dimensional reconstruction. A rod terminal normally showed the presence of 1 synaptic complex consisting of a single synaptic ribbon located between 2 processes of horizontal cells and 2 bipolar cell dendrites. In a rod terminal showing an enlarged synaptic complex, 2 or 3 separate synaptic ribbons formed the centres of separate synaptic sites; each of the sites was characterized by the presence of 2 laterally placed horizontal cell processes and 2 bipolar cell dendrites. However, these processes from the multiple synaptic sites were observed to arise from the 2 horizontal and the 2 bipolar cell elements that were normally present in the rod terminal. Thus proliferation of synaptic sites in the rod terminals occurred through growth and sprouting from the processes of the second order neuronal components present within the terminals. The altered synaptic complexes in the variously affected groups were structurally comparable and appeared to have resulted from similar microanatomical changes. The increase in the frequency of rod terminals with multiple synaptic sites occurred as a sequel to increasing photoreceptor cell loss that was recorded at different age points in the different experimental groups. It is concluded that rod synapses in the adult mammalian retina possess structural plasticity that permits compensatory growth. Microsc Res Tech 36:96–105, 1997. © 1997 Wiley‐Liss, Inc.

Synaptic Plasticity in Mammalian Photoreceptors Prepared as Sheets for Retinal Transplantation

“…Retraction of photoreceptor terminals and subsequent neurite extension have also been seen in studies of experimental retinal detachment and reattachment 18,25 (Lewis GP, et al IOVS 2002;43:ARVO E-Abstract 4540). In addition, reactive sprouting and/or synaptogenesis by photoreceptors has been observed in several animal models of retinal degeneration, including the light-damaged mouse retina, 27,29 the rd and rds mouse, 26,28,29,34,43 and the rhodopsin Pro347Leu transgenic pig, 34 and in human donor retinas from eyes with retinitis pigmentosa. 30,32,44 Thus, it is evident that adult photoreceptor terminals are capable of structural plasticity.…”

“…9,19 -24 Adult tissue was chosen because mature photoreceptor sheets have shown comparable results to those of immature sheets when transplanted into the subretinal space 9,20,23 especially when transvitreal grafting procedures were used. 1 Moreover, the presynaptic plasticity displayed by adult photoreceptors during disease 18,[25][26][27][28][29][30][31][32][33][34] and in culture 17,35,36 supports the notion that adult photoreceptors are capable of synapse formation after transplantation. Finally, the porcine retina was used because the anatomy, size, and vasculature of the porcine eye are close to those of the human, [37][38][39] and the porcine retina is well endowed with cones that form an area centralis.…”

Cyclic AMP Prevents Retraction of Axon Terminals in Photoreceptors Prepared for Transplantation: An In Vitro Study

“…However, the scarcity of neural process outgrowth from transplanted photoreceptors as well as the absence of definite synaptic contacts with the appropriate host second-order neurons is a recurring result in all transplantation paradigms, regardless of the type of preparation or age of donor tissue. [1][2][3][4][5] The apparent lack of synaptic regeneration by transplanted photoreceptors contrasts with the growth of processes by both rod and cone photoreceptors and by other cells of the retina after isolation in culture, 6 -8 in experimental retinal detachment and reattachment, 9,10 and during retinal degeneration in both animal models [11][12][13][14][15] and human disease. 16 In these cases, second-order neurons extend elaborate dendrites, and rod and cone cells grow neurites and form numerous presynaptic varicosities.…”

Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice

“…Synapse turnover in older animals is suggested by the absence of SBs at 22% of the PSDs and a larger incidence of multiple SBs. The increased incidence of synapses with multiple SBs is also observed in the mouse retina following partial photoreceptor loss (Jansen et al, 1997), suggestive of a reactive response to neural damage. These predominantly pre-synaptic changes could conceivably be induced within the cell by changes in vesicle recycling or extrinsically by efferent input to the IHC.…”