title: Role of crystallins in ocular neuroprotection and axonal regeneration.
abstract: Neuroprotection is an emerging challenge in ophthalmology due to the particularly exposed location of retinal neurons and to the steadily increasing rate of intraocular surgical and pharmacological treatments applied to various eye diseases. Within few decades neuroprotection has developed from strongly contested approaches to being recognized and introduced as a potentially clinical application. One of the groups of putative substances for neuroprotection comprises αA- and αB-crystallins, which are types of heat-shock proteins and are considered to be molecular chaperones. The β/γ-crystallins form their own superfamily and are characterized as proteins with a distinct structure containing four Greek key motifs. Besides being abundant in the ocular lens, crystallins are also expressed in both the developing and mature retina. Crystallins are dramatically up-regulated in numerous retinal pathologies, including mechanical injury, ischemic insults, age-related macular degeneration, uveoretinitis, and diabetic retinopathy. Crystallins of the α family are thought to play a crucial role in retinal neuron survival and inflammation. Crystallins of the β/γ superfamily are also small proteins with a possible emerging role in retinal tissue remodeling and repair. One of the typical retinal diseases associated with crystallins is the experimental glaucomatous neuropathy that is characterized by their expression. Another typical retinal disease is the atrophy that occurs after mechanical injury to the optic nerve, which is associated with the need to regrow retinal axons. We have shown in regenerative models in vivo and in vitro that βB2-crystallin actively supports the regenerative growth of cut retinal axons, thereby offering targets for neuroprotective and regenerative treatments. In this review we discuss the discovery that βB2-crystallin is clearly up-regulated in the regenerating retina in vitro. βB2-Crystallin is produced and secreted during axon elongation, while β/γ-crystallins promote axon growth both in vivo and in vitro by acting either directly by uptake into cells, or indirectly by enhancing the production of ciliary neurotrophic factor from astrocytes to synergistically promote axon regrowth. We also discuss methods to induce the continuous production of crystallins at the site of injury and repair based on the use of transfected neural progenitor cells. This review ultimately leads to the conclusion that the postinjury fate of neurons cannot be seen merely as inevitable, but instead should be regarded as a challenge to shaping the neuroprotective and regenerative conditions that promote cell survival and axon repair.
authors.affiliation: Institute of Experimental Ophthalmology, Germany; Center of Excellence "Cells in Motion" (CiM), School of Medicine, University of Münster, Albert-Schweitzer-Campus 1, D15, 48149 Münster, Germany. Electronic address: solon@uni-muenster.de.
authors.forename: Solon
authors.initials: S
authors.lastname: Thanos
authors.affiliation: Institute of Experimental Ophthalmology, Germany; Center of Excellence "Cells in Motion" (CiM), School of Medicine, University of Münster, Albert-Schweitzer-Campus 1, D15, 48149 Münster, Germany.
authors.forename: Michael R R
authors.initials: MR
authors.lastname: Böhm
authors.affiliation: Massachusetts Eye and Ear Infirmary (MEEI), Boston, MA, USA; Eye Clinics, University Essen, Germany.
authors.forename: Melissa
authors.initials: M
authors.lastname: Meyer zu Hörste
authors.affiliation: Institute of Experimental Ophthalmology, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Prokosch-Willing
authors.affiliation: Departement of Ophthalmology at Franziskus Hospital Münster, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Hennig
authors.affiliation: Departement of Ophthalmology at Franziskus Hospital Münster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bauer
authors.affiliation: Institute of Experimental Ophthalmology, Germany; Departement of Ophthalmology at Franziskus Hospital Münster, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Heiligenhaus
mesh_terms: D001369:Axons / Q000473:pathology / Q000502:physiology*; D003459:Crystallins / Q000502:physiology*; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D012160:Retina / Q000502:physiology*; D012164:Retinal Diseases / Q000503:physiopathology*
chemical_list: D003459:Crystallins
keywords: Axonal regrowth; Crystallins; Glaucoma injury; Neuroprotection; Retina