XB-ART-5827Dev Dyn February 1, 2003; 226 (2): 211-24.
Eye regeneration at the molecular age.
Eye tissues such as the lens and the retina possess remarkable regenerative abilities. In amphibians, a complete lens can be regenerated after lentectomy. The process is a classic example of transdifferentiation of one cell type to another. Likewise, retina can be regenerated, but the strategy used to replace the damaged retina differs, depending on the animal system and the age of the animal. Retina can be regenerated by transdifferentiation or by the use of stem cells. In this review, we present a synthesis on the regenerative capacity of eye tissues in different animals with emphasis on the strategy and the molecules involved. In addition, we stress the place of this field at the molecular age and the importance of the recent technologic advances.
PubMed ID: 12557200
Article link: Dev Dyn
Genes referenced: fgf1
Article Images: [+] show captions
|Figure 1. Series of histologic sections depicting the process of lens regeneration in the adult newt. A: Dorsal iris 10 days after lentectomy. The tip of the dorsal iris (arrowhead) has depigmented and dedifferentiated. This finding is the beginning of the formation of the lens vesicle. B: Dorsal iris 15 days after lentectomy. The internal layer of the lens vesicle thickens, and differentiation of the lens fibers starts. C: Regenerating lens 20 days after lentectomy. Lens differentiation is almost complete. The lens epithelium is covering the lens in the anterior, whereas lens fiber differentiation is prominent in the posterior part of the lens. D: Regenerated lens 25 days after lentectomy showing a definite lens. The purple color of the regenerating lens vesicle/lens in A–C is due to detection of FGF-1 expression and, in D, is due to detection of gamma crystallin. Note in D that the lens epithelium is negative for the lens fiber-specific gamma crystallin. From Tsonis, PA (1998; Regeneration of the Vertebrate Lens and Other Eye Structures. In: Encyclopedia of Life Sciences, pp. 164–169. London: Nature Publishing Group. [doi: 10.1038/npg.els.0001102] www.els.net).Download figure to PowerPoint|
|Figure 2. Implantation of dorsal and ventral aggregates into a lentectomized newt eye collected 20 days later. A: Dorsal aggregate was implanted. B: Ventral aggregate was implanted. Note that the dorsal aggregate differentiated into a lens vesicle (arrow in A), whereas the ventral stayed as a mass of pigmented cells (arrow in B). The host lens (arrowheads in A,B) regenerated normally from the dorsal iris.Download figure to PowerPoint|
|Figure 3. Diagram of a vertebrate eye pinpointing the regions of the retina that contribute to the process of retina regeneration in the different model organisms. #1: Retinal pigment epithelium (RPE, red) can transdifferentiate into neural retina in a many embryonic species, but as adult only in the newt. #2: Ciliary marginal zone (CMZ, blue) is a source of stem cells and precursors that contribute to the ongoing growth of the retina as well as during regeneration in many organisms. #3: Rod precursors (red/spherical) contribute to rod photoreceptor regeneration in teleost fish. #4: Intrinsic stem cells (red/fusiform) present in the inner nuclear layer (INL) that proliferate and give rise to neural progenitors that migrate to the outer nuclear layer (ONL) and replace damaged retinal cells. #5: Müller glia cells (red/cell body and axons) that proliferate and migrate to the ONL to replace damaged retina. #6: pigmented cells of the ciliary margin (PCM, pink) cells can transdifferentiate in vitro in mice. GCL, ganglion cell layer; CGZ, circumferential germinal zone.|
|Figure 4. Representation of the structure of the vertebrate retina. All retinal layers are represented in the illustration and correspond to the layers of the adjacent section from a newt eye. From Litzinger, TC, and Del Rio-Tsonis, K (2001; Eye Anatomy. In: Encyclopedia of Life Sciences. London: Nature Publishing Group. [doi:10.1038/npg.els.0000108] http://www.els.net/).Download figure to PowerPoint|
|Figure 5. Retina regeneration in adult newts. A: Intact retina section showing all the layers of a mature retina. B: Retinectomized newt eye (5 days postretinectomy). Here, dedifferentiation and proliferation of the retinal pigmented epithelial cells begin. Note that the cells shown by arrowheads have dedifferentiated or are in the process of dedifferentiation. C: After approximately 2 weeks postretinectomy a neuroepithelial (ne) cell layer forms that will eventually give rise to all the cells of the retina. D: A month postretinectomy, the regenerated differentiated retina stratifies into the different retinal layers: the outer nuclear layer (o), the inner nuclear layer (i), and the ganglion cell layer (g). The retinal pigment epithelium (RPE) has also been renewed, and the orientation of the newly formed retina is the same as the intact. Sections were stained with hematoxylin and eosin.Download figure to PowerPoint|
|Figure 6. Retina regeneration in embryonic chick eyes. A: Intact chick eye at day 4 of development (stages 22–24 of development according to Hamburger and Hamilton, 1951). Note the retina (r) is not fully formed yet and the retinal pigment epithelium (RPE) does not appear pigmented. B: Retinectomized chick eye at day 4 of development. The entire neural retina has been removed, and the RPE layer has thickened. C: Intact eye at day 7 of development. The neuroepithelial layer has thickened (represented here by r), but no layers have been formed yet. D: At 3 days postretinectomy (day 7 of development), the RPE at the posterior region of the eye has transdifferentiated (t) to form a neuroepithelium similar to the one present in the intact eye at the equivalent stage (C). E: Intact eye at 11 days of development. Note all the retinal layers are nicely formed by now: the outer nuclear layer (o), the inner nuclear layer (i), and the ganglion cell layer (g). F: Regenerating retina 7 days postretinectomy (11 days of development), at which time, new retina has been formed by means of the transdifferentiation of the RPE (t) or by means of the use of neural precursors from the ciliary marginal zone (m). Note that the inner loop of regenerated retina contains all the retinal cell layers in the original orientation, whereas the retina regenerated by means of transdifferentiation of the RPE has a reversed or mirrored orientation. l, lens. Sections were stained with hematoxylin and eosin.Download figure to PowerPoint|